Current Research and Scholarly Interests


My research interests focus on the design and discovery of synthetic, and natural product inspired small molecules which can be used as probes for developing understanding of biological phenomena, including protein-protein interactions and modulation of signal transduction pathways. My laboratory employs the tools of synthetic medicinal chemistry, molecular modeling and chemical biology for translational research in drug discovery, development, imaging and radiation.

Stanford Advisees


All Publications


  • 1,4-Substituted Triazoles as Nonsteroidal Anti-Androgens for Prostate Cancer Treatment JOURNAL OF MEDICINAL CHEMISTRY Ferroni, C., Pepe, A., Kim, Y. S., Lee, S., Guerrini, A., Parenti, M. D., Tesei, A., Zamagni, A., Cortesi, M., Zaffaroni, N., De Cesare, M., Beretta, G. L., Trepel, J. B., Malhotra, S. V., Varchi, G. 2017; 60 (7): 3082-3093

    Abstract

    Prostate cancer (PC) is the fifth leading cause of cancer death in men, and the androgen receptor (AR) represents the primary target for PC treatment, even though the disease frequently progresses toward androgen-independent forms. Most of the commercially available nonsteroidal antiandrogens show a common scaffold consisting of two aromatic rings connected by a linear or a cyclic spacer. By taking advantage of a facile, one-pot click chemistry reaction, we report herein the preparation of a small library of novel 1,4-substituted triazoles with AR antagonistic activity. Biological and theoretical evaluation demonstrated that the introduction of the triazole core in the scaffold of nonsteroidal antiandrogens allowed the development of small molecules with improved overall AR-antagonist activity. In fact, compound 14d displayed promising in vitro antitumor activity toward three different prostate cancer cell lines and was able to induce 60% tumor growth inhibition of the CW22Rv1 in vivo xenograft model. These results represent a step toward the development of novel and improved AR antagonists.

    View details for DOI 10.1021/acs.jmedchem.7b00103

    View details for Web of Science ID 000399436100032

    View details for PubMedID 28272894

  • Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation of p53-miR34a axis. Molecular oncology Avtanski, D. B., Nagalingam, A., Tomaszewski, J. E., Risbood, P., Difillippantonio, M. J., Saxena, N. K., Malhotra, S. V., Sharma, D. 2016; 10 (7): 1118-1132

    Abstract

    The tumor suppressor p53 plays a critical role in suppressing cancer growth and progression and is an attractive target for the development of new targeted therapies. We synthesized several indolo-pyrido-isoquinolin based alkaloids to activate p53 function and examined their therapeutic efficacy using NCI-60 screening. Here, we provide molecular evidence that one of these compounds, 11-methoxy-2,3,4,13-tetrahydro-1H-indolo[2',3':3,4]pyrido[1,2-b]isoquinolin-6-ylium-bromide (termed P18 or NSC-768219) inhibits growth and clonogenic potential of cancer cells. P18 treatment results in downregulation of mesenchymal markers and concurrent upregulation of epithelial markers as well as inhibition of migration and invasion. Experimental epithelial-mesenchymal-transition (EMT) induced by exposure to TGFβ/TNFα is also completely reversed by P18. Importantly, P18 also inhibits mammosphere-formation along with a reduction in the expression of stemness factors, Oct4, Nanog and Sox2. We show that P18 induces expression, phosphorylation and accumulation of p53 in cancer cells. P18-mediated induction of p53 leads to increased nuclear localization and elevated expression of p53 target genes. Using isogenic cancer cells differing only in p53 status, we show that p53 plays an important role in P18-mediated alteration of mesenchymal and epithelial genes, inhibition of migration and invasion of cancer cells. Furthermore, P18 increases miR-34a expression in p53-dependent manner and miR-34a is integral for P18-mediated inhibition of growth, invasion and mammosphere-formation. miR-34a mimics potentiate P18 efficacy while miR-34a antagomirs antagonize P18. Collectively, these data provide evidence that P18 may represent a promising therapeutic strategy for the inhibition of growth and progression of breast cancer and p53-miR-34a axis is important for P18 function.

    View details for DOI 10.1016/j.molonc.2016.04.003

    View details for PubMedID 27259808

  • Imidazolium-derived ionic salts induce inhibition of cancerous cell growth through apoptosis MEDCHEMCOMM Malhotra, S. V., Kumar, V., Velez, C., Zayas, B. 2014; 5 (9): 1404-1409

    View details for DOI 10.1039/c4md00161c

    View details for Web of Science ID 000341017700018

  • NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation JOURNAL OF CLINICAL INVESTIGATION Kim, J., Thimmulappa, R. K., Kumar, V., Cui, W., Kumar, S., Kombairaju, P., Zhang, H., Margolick, J., Matsui, W., MacVittie, T., Malhotra, S. V., Biswal, S. 2014; 124 (2): 730-741

    Abstract

    A nuclear disaster may result in exposure to potentially lethal doses of ionizing radiation (IR). Hematopoietic acute radiation syndrome (H-ARS) is characterized by severe myelosuppression, which increases the risk of infection, bleeding, and mortality. Here, we determined that activation of nuclear factor erythroid-2-related factor 2 (NRF2) signaling enhances hematopoietic stem progenitor cell (HSPC) function and mitigates IR-induced myelosuppression and mortality. Augmenting NRF2 signaling in mice, either by genetic deletion of the NRF2 inhibitor Keap1 or by pharmacological NRF2 activation with 2-trifluoromethyl-2'-methoxychalone (TMC), enhanced hematopoietic reconstitution following bone marrow transplantation (BMT). Strikingly, even 24 hours after lethal IR exposure, oral administration of TMC mitigated myelosuppression and mortality in mice. Furthermore, TMC administration to irradiated transgenic Notch reporter mice revealed activation of Notch signaling in HSPCs and enhanced HSPC expansion by increasing Jagged1 expression in BM stromal cells. Administration of a Notch inhibitor ablated the effects of TMC on hematopoietic reconstitution. Taken together, we identified a mechanism by which NRF2-mediated Notch signaling improves HSPC function and myelosuppression following IR exposure. Our data indicate that targeting this pathway may provide a countermeasure against the damaging effects of IR exposure.

    View details for DOI 10.1172/JCI70812

    View details for Web of Science ID 000331413300032

    View details for PubMedID 24463449

  • Identification of the First Inhibitor of the GBP1:PIM1 Interaction. Implications for the Development of a New Class of Anticancer Agents against Paclitaxel Resistant Cancer Cells Journal of Medicinal Chemistry Andreoli, ., Persico, M., Kumar, A., Orteca, N., Kumar, V., Pepe , A., Mahalingam, S., Alegria,, . E., Petrella, L., Sevciunaite, L., Camperchioli, A., Mariani, M., Di Dato, ., Novellino, E., Scambia, G., Malhotra, S. V., Ferlini, C., Fattorusso, C. 2014; 57 (19): 7916-7932

    View details for DOI 10.1021/jm5009902

  • Synthesis and Structure-Activity Relationship Studies of Novel Dihydropyridones as Androgen Receptor Modulators JOURNAL OF MEDICINAL CHEMISTRY Pepe, A., Pamment, M., Kim, Y. S., Lee, S., Lee, M., Beebe, K., Filikov, A., Neckers, L., Trepel, J. B., Malhotra, S. V. 2013; 56 (21): 8280-8297

    Abstract

    A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeling and molecular mechanics were used to build a structural model of the androgen receptor-ligand binding domain and to investigate the structural basis of the antagonism. The model is qualitatively consistent with the observed SAR. Moreover, the enrichment plot shows that screening with the model performs significantly better than random screening. Therefore, the model probably represents a realistic conformation of the antagonist form and can be utilized for structure-based design of novel antiandrogens.

    View details for DOI 10.1021/jm301714s

    View details for Web of Science ID 000327111100005

    View details for PubMedID 24044500

  • Methoxychalcone inhibitors of androgen receptor translocation and function BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Kim, Y. S., Kumar, V., Lee, S., Iwai, A., Neckers, L., Malhotra, S. V., Trepel, J. B. 2012; 22 (5): 2105-2109

    Abstract

    Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non-responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity.

    View details for DOI 10.1016/j.bmcl.2011.12.141

    View details for Web of Science ID 000300451200053

    View details for PubMedID 22310230

  • Application of silver N-heterocyclic carbene complexes in O-glycosidation reactions CARBOHYDRATE RESEARCH Talisman, I. J., Kumar, V., Deschamps, J. R., Frisch, M., Malhotra, S. V. 2011; 346 (15): 2337-2341

    Abstract

    We report the efficient O-glycosidation of glycosyl bromides with therapeutically relevant acceptors facilitated by silver N-heterocyclic carbene (Ag-NHC) complexes. A set of four Ag-NHC complexes was synthesized and evaluated as promoters for glycosidation reactions. Two new bis-Ag-NHC complexes derived from ionic liquids 1-benzyl-3-methyl-1H-imidazolium chloride and 1-(2-methoxyethyl)-3-methylimidazolium chloride were found to efficiently promote glycosidation, whereas known mono-Ag complexes of 1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride and 1,3-bis(2,6-di-isopropylphenyl)imidazolium chloride failed to facilitate the reaction. The structures of the promoters were established by X-ray crystallography and these complexes were employed in the glycosidation of different glycosyl bromide donors with biologically valuable acceptors, such as estrone, estradiol, and various flavones. The products were obtained in yields considered good to excellent, and all reactions were highly selective for the β isomer regardless of neighboring group effects.

    View details for DOI 10.1016/j.carres.2011.07.025

    View details for Web of Science ID 000296950400003

    View details for PubMedID 21911215

  • N-Hydroxyethyl-4-aza-didehydropodophyllotoxin derivatives as potential antitumor agents EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES Kumar, A., Kumar, V., Alegria, A. E., Malhotra, S. V. 2011; 44 (1-2): 21-26

    Abstract

    Three different series of N-hydroxyethyl aza-podophyllotoxin derivatives containing (i) a five-membered methylenedioxy ring (7a-f), (ii) a five-membered ring with no heteroatom (8a-f) or (iii) a six membered ethylenedioxy ring (9a-f) as ring A were synthesized using a convenient one-pot multi-component reaction. Further variation on ring E was done by decorating it with methoxy and hydroxy groups at different positions. Calculation of logP values of these compounds indicates them to be better soluble than corresponding non-hydroxy derivatives. These novel aza-podophyllotoxin derivatives were screened for their cytostatic and cytotoxic activities on National Cancer Institute's 60 human tumor cell lines to study the structure activity relationship. The overall anticancer activity of these compounds was in the order of 8a-f>9a-f>7a-f. Furthermore, the compounds having 3'-methoxy and 3',4',5'-trimethoxy substitution at ring E were the most active within the series. The cytotoxicity of all the active compounds was low, while their antiproliferative (or cytostatic) activity was high, providing a wide therapeutic window for their potential application as anticancer drugs.

    View details for DOI 10.1016/j.ejps.2011.04.013

    View details for Web of Science ID 000295109400003

    View details for PubMedID 21601635

  • Novel Chalcone Derivatives as Potent Nrf2 Activators in Mice and Human Lung Epithelial Cells JOURNAL OF MEDICINAL CHEMISTRY Kumar, V., Kumar, S., Hassan, M., Wu, H., Thimmulappa, R. K., Kumar, A., Sharma, S. K., Parmar, V. S., Biswal, S., Malhotra, S. V. 2011; 54 (12): 4147-4159

    Abstract

    Nrf2-mediated activation of antioxidant response element is a central part of molecular mechanisms governing the protective function of phase II detoxification and antioxidant enzymes against carcinogenesis, oxidative stress, and inflammation. Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. We have designed and synthesized novel chalcone derivatives as Nrf2 activators. The potency of these compounds was measured by the expression of Nrf2 dependent antioxidant genes GCLM, NQO1, and HO1 in human lung epithelial cells, while the cytotoxicity was analyzed using MTT assay. In vivo potency of identified lead compounds to activate Nrf2 was evaluated using a mouse model. Our studies showed 2-trifluoromethyl-2'-methoxychalone (2b) to be a potent activator of Nrf2, both in vitro and in mice. Additional experiments showed that the activation of Nrf2 by this compound is independent of reactive oxygen species or redox changes. We have discussed a quantitative structure-activity relationship and proposed a possible mechanism of Nrf2 activation.

    View details for DOI 10.1021/jm2002348

    View details for Web of Science ID 000291709100013

    View details for PubMedID 21539383

  • Synthesis of Fused Bicyclic Systems with Nitrogen Atom at the Bridgehead, Including Indolizidines and Quinolizidines JOURNAL OF ORGANIC CHEMISTRY Pepe, A., Pamment, M., Georg, G. I., Malhotra, S. V. 2011; 76 (9): 3527-3530

    Abstract

    Monocyclic as well as fused bicyclic systems with a nitrogen 10 atom at the bridgehead, including indolizidines and quinolizidines, can be prepared in four steps from N-Boc β-lactams. These easily prepared, highly robust, and flexible building blocks allow the incorporation of chirality and structural diversity, rendering the method feasible for diversity- as well as target-oriented synthesis.

    View details for DOI 10.1021/jo102558u

    View details for Web of Science ID 000289956900063

    View details for PubMedID 21452823

  • Quantitative Proteomic Profiling Reveals Key Pathways in the Anticancer Action of Methoxychalcone Derivatives in Triple Negative Breast Cancer. Journal of proteome research Going, C. C., Tailor, D., Kumar, V., Birk, A. M., Pandrala, M., Rice, M. A., Stoyanova, T., Malhotra, S., Pitteri, S. J. 2018

    Abstract

    Triple negative breast cancer is an aggressive, heterogeneous disease with high recurrence and metastasis rates even with modern chemotherapy regimens and thus is in need of new therapeutics. Here, three novel synthetic analogues of chalcones, plant-based molecules that have demonstrated potency against a wide variety of cancers, were investigated as potential therapeutics for triple negative breast cancer. These compounds exhibit IC50 values of 5 muM in triple negative breast cancer cell lines and are more potent against triple negative breast cancer cell lines than against nontumor breast cell lines according to viability experiments. Tandem mass tag-based quantitative proteomics followed by gene set enrichment analysis and validation experiments using flow cytometry, apoptosis, and Western blot assays revealed three different anticancer mechanisms for these compounds. First, the chalcone analogues induce the unfolded protein response followed by apoptosis. Second, increases in the abundances of MHC-I pathway proteins occurs, which would likely result in immune stimulation in an organism. And third, treatment with the chalcone analogues causes disruption of the cell cycle by interfering with microtubule structure and by inducing G1 phase arrest. These data demonstrate the potential of these novel chalcone derivatives as treatments for triple negative breast cancer, though further work evaluating their efficacy in vivo is needed.

    View details for DOI 10.1021/acs.jproteome.8b00636

    View details for PubMedID 30200768

  • Small molecules facilitating DNA repair in breast cancer cells Pandrala, M., Hastak, K., Kumar, V., Gardiner, M., Ford, J., Malhotra, S. AMER CHEMICAL SOC. 2018
  • Novel chalcone derivatives as potential therapeutic agents for triple negative breast cancer Kumar, V., Going, C., Tailor, D., Pandrala, M., Birk, A., Pitteri, S., Malhotra, S. AMER CHEMICAL SOC. 2018
  • Indole-based positive allosteric modulators for targeting CB1 receptor to overcome neuropathic pain Resendez, A., Kumar, K., Kumar, V., Kobilka, B., Malhotra, S. AMER CHEMICAL SOC. 2018
  • Synthesis and evaluation of structure-activity based derivatives of ERGi-USU, a selective inhibitor for ERG-positive prostate cancer cells. Mohamed, A. A., Xavier, C. P., Sukumar, G., Tan, S., Ravindranath, L., Sreenath, T. L., McLeod, D. G., Rosner, I. L., Petrovics, G., Srivastava, M., Strovel, J., Dalgard, C. L., Malhotra, S. V., Dobi, A., Srivastava, S. AMER ASSOC CANCER RESEARCH. 2018: 76–77
  • Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer CANCER RESEARCH Moses, M. A., Kim, Y., Rivera-Marquez, G. M., Oshima, N., Watson, M. J., Beebe, K. E., Wells, C., Lee, S., Zuehlke, A. D., Shao, H., Bingman, W. E., Kumar, V., Malhotra, S. V., Weigel, N. L., Gestwicki, J. E., Trepel, J. B., Neckers, L. M. 2018; 78 (14): 4022–35

    Abstract

    Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling, in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small-molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with Hsp40. Pull-down studies using biotinylated-C86 found Hsp40 present in a multiprotein complex with full-length (FL-) AR, ARv7, and Hsp70 in CRPC cells. Treatment of CRPC cells with C86 or the allosteric Hsp70 inhibitor JG98 resulted in rapid protein destabilization of both FL-AR and ARv, including ARv7, concomitant with reduced FL-AR- and ARv7-mediated transcriptional activity. The glucocorticoid receptor, whose elevated expression in a subset of CRPC also leads to androgen-independent AR target gene transcription, was also destabilized by inhibition of Hsp40 or Hsp70. In vivo, Hsp40 or Hsp70 inhibition demonstrated single-agent and combinatorial activity in a 22Rv1 CRPC xenograft model. These data reveal that, in addition to recognized roles of Hsp40 and Hsp70 in FL-AR LBD remodeling, ARv lacking the LBD remain dependent on molecular chaperones for stability and function. Our findings highlight the feasibility and potential benefit of targeting the Hsp40/Hsp70 chaperone axis to treat prostate cancer that has become resistant to standard antiandrogen therapy.Significance: These findings highlight the feasibility of targeting the Hsp40/Hsp70 chaperone axis to treat CRPC that has become resistant to standard antiandrogen therapy. Cancer Res; 78(14); 4022-35. ©2018 AACR.

    View details for DOI 10.1158/0008-5472.CAN-17-3728

    View details for Web of Science ID 000439199100023

    View details for PubMedID 29764864

    View details for PubMedCentralID PMC6050126

  • Identification of a Small Molecule That Selectively Inhibits ERG-Positive Cancer Cell Growth CANCER RESEARCH Mohamed, A. A., Xavier, C. P., Sukumar, G., Tan, S., Ravindranath, L., Seraj, N., Kumar, V., Sreenath, T., McLeod, D. G., Petrovics, G., Rosner, I. L., Srivastava, M., Strovel, J., Malhotra, S. V., LaRonde, N. A., Dobi, A., Dalgard, C. L., Srivastava, S. 2018; 78 (13): 3659–71

    Abstract

    Oncogenic activation of the ETS-related gene (ERG) by recurrent gene fusions (predominantly TMPRSS2-ERG) is one of the most validated and prevalent genomic alterations present in early stages of prostate cancer. In this study, we screened small-molecule libraries for inhibition of ERG protein in TMPRSS2-ERG harboring VCaP prostate cancer cells using an In-Cell Western Assay with the highly specific ERG-MAb (9FY). Among a subset of promising candidates, 1-[2-Thiazolylazo]-2-naphthol (NSC139021, hereafter ERGi-USU) was identified and further characterized. ERGi-USU selectively inhibited growth of ERG-positive cancer cell lines with minimal effect on normal prostate or endothelial cells or ERG-negative tumor cell lines. Combination of ERGi-USU with enzalutamide showed additive effects in inhibiting growth of VCaP cells. A screen of kinases revealed that ERGi-USU directly bound the ribosomal biogenesis regulator atypical kinase RIOK2 and induced ribosomal stress signature. In vivo, ERGi-USU treatment inhibited growth of ERG-positive VCaP tumor xenografts with no apparent toxicity. Structure-activity-based derivatives of ERGi-USU recapitulated the ERG-selective activity of the parental compound. Taken together, ERGi-USU acts as a highly selective inhibitor for the growth of ERG-positive cancer cells and has potential for further development of ERG-targeted therapy of prostate cancer and other malignancies.Significance: A highly selective small-molecule inhibitor of ERG, a critical driver of early stages of prostate cancer, will be imperative for prostate cancer therapy. Cancer Res; 78(13); 3659-71. ©2018 AACR.

    View details for DOI 10.1158/0008-5472.CAN-17-2949

    View details for Web of Science ID 000437214300021

    View details for PubMedID 29712692

  • Molecular Imaging Biosensor Monitors p53 Sumoylation in Cells and Living Mice ANALYTICAL CHEMISTRY Sekar, T. V., Foygel, K., Devulapally, R., Kumar, V., Malhotra, S., Massoud, T. F., Paulmurugan, R. 2016; 88 (23): 11420-11428

    Abstract

    Small molecule mediated stabilization of p53 tumor suppressor protein through sumoylation is a promising new strategy for improving cancer chemotherapy. A molecular tool that monitors p53 sumoylation status and expedites screening for drugs that enhance p53 sumoylation would be beneficial. We report a molecularly engineered reporter fragment complementation biosensor based on optical imaging of Firefly luciferase (FLuc), to quantitatively image p53 sumoylation and desumoylation in cells and living mice. We initially characterized this biosensor by successfully imaging sumoylation of several target proteins, achieving significant FLuc complementation for ERα (p < 0.01), p53 (p < 0.005), FKBP12 (p < 0.03), ID (p < 0.03), and HDAC1 (p < 0.002). We then rigorously tested the sensitivity and specificity of the biosensor using several variants of p53 and SUMO1, including deletion mutants, and those with modified sequences containing the SUMO-acceptor site of target proteins. Next we evaluated the performance of the biosensor in HepG2 cells by treatment with ginkgolic acid, a drug that reduces p53 sumoylation, as well as trichostatin A, a potential inducer of p53 sumoylation by enhancement of its nuclear export. Lastly, we demonstrated the in vivo utility of this biosensor in monitoring and quantifying the effects of these drugs on p53 sumoylation in living mice using bioluminescence imaging. Adoption of this biosensor in future high throughput drug screening has the important potential to help identify new and repurposed small molecules that alter p53 sumoylation, and to preclinically evaluate candidate anticancer drugs in living animals.

    View details for DOI 10.1021/acs.analchem.6b02048

    View details for Web of Science ID 000389556900027

    View details for PubMedID 27934110

  • C-5-curcuminoid-4-aminoquinoline based molecular hybrids: design, synthesis and mechanistic investigation of anticancer activity NEW JOURNAL OF CHEMISTRY Kandi, S. K., Manohar, S., Gerena, C. E., Zayas, B., Malhotra, S. V., Rawat, D. S. 2015; 39 (1): 224-234

    View details for DOI 10.1039/c4nj00936c

    View details for Web of Science ID 000348331900030

  • Imidazole derivatives show anticancer potential by inducing apoptosis and cellular senescence MEDCHEMCOMM Sharma, G. V., Ramesh, A., Singh, A., Srikanth, G., Jayaram, V., Duscharla, D., Jun, J. H., Ummanni, R., Malhotra, S. V. 2014; 5 (11): 1751-1760

    View details for DOI 10.1039/c4md00277f

    View details for Web of Science ID 000344320700019

  • Identification of the First Inhibitor of the GBP1:PIM1 Interaction. Implications for the Development of a New Class of Anticancer Agents against Paclitaxel Resistant Cancer Cells JOURNAL OF MEDICINAL CHEMISTRY Andreoli, M., Persico, M., Kumar, A., Orteca, N., Kumar, V., Pepe, A., Mahalingam, S., Alegria, A. E., Petrella, L., Sevciunaite, L., Camperchioli, A., Mariani, M., Di Dato, A., Novellino, E., Scambia, G., Malhotra, S. V., Ferlini, C., Fattorusso, C. 2014; 57 (19): 7916-7932

    Abstract

    Class III β-tubulin plays a prominent role in the development of drug resistance to paclitaxel by allowing the incorporation of the GBP1 GTPase into microtubules. Once in the cytoskeleton, GBP1 binds to prosurvival kinases such as PIM1 and initiates a signaling pathway that induces resistance to paclitaxel. Therefore, the inhibition of the GBP1:PIM1 interaction could potentially revert resistance to paclitaxel. A panel of 44 4-azapodophyllotoxin derivatives was screened in the NCI-60 cell panel. The result is that 31 are active and the comparative analysis demonstrated specific activity in paclitaxel-resistant cells. Using surface plasmon resonance, we were able to prove that NSC756093 is a potent in vitro inhibitor of the GBP1:PIM1 interaction and that this property is maintained in vivo in ovarian cancer cells resistant to paclitaxel. Through bioinformatics, molecular modeling, and mutagenesis studies, we identified the putative NSC756093 binding site at the interface between the helical and the LG domain of GBP1. According to our results by binding to this site, the NSC756093 compound is able to stabilize a conformation of GBP1 not suitable for binding to PIM1.

    View details for DOI 10.1021/jm50099021

    View details for Web of Science ID 000343016300008

    View details for PubMedID 25211704

  • Novel 3,5-bis(arylidiene)-4-piperidone based monocarbonyl analogs of curcumin: anticancer activity evaluation and mode of action study MEDCHEMCOMM Thakur, A., Manohar, S., Gerena, C. E., Zayas, B., Kumar, V., Malhotra, S. V., Rawat, D. S. 2014; 5 (5): 576-586

    View details for DOI 10.1039/c3md00399j

    View details for Web of Science ID 000335011900003

  • Synthesis and anticancer activity evaluation of resveratrol-chalcone conjugates MEDCHEMCOMM Kumar, D., Raj, K. K., Malhotra, S. V., Rawat, D. S. 2014; 5 (4): 528-535

    View details for DOI 10.1039/c3md00329a

    View details for Web of Science ID 000333580000017

  • Toxicity of ionic liquids to Clostridium sp. and effects on uranium biosorption JOURNAL OF HAZARDOUS MATERIALS Zhang, C., Malhotra, S. V., Francis, A. J. 2014; 264: 246-253

    Abstract

    As green solvents ionic liquids (ILs) show high potential in nuclear industry for extraction and purification of actinides. However, to date relatively little information has been gained on ILs application in microbial processes, for example biosorption of radionuclides. We investigated the effects of three ILs, 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6), N-ethylpyridinium trifluoroacetate (EtPyCF3COO) and N-ethylpyridinium tetrafluoroborate (EtPyBF4) on the growth and biosorption of uranium by Clostridium sp. The ILs affected the growth of the bacterium as evidenced by decreases in optical density, total gas production, and organic acids production from glucose metabolism. The IC50-48h of three ILs decreased in the order of BMIMPF6 (8.26mM)>EtPyBF4 (7.04mM)>EtPyCF3COO (4.05mM). Uranium biosorption by the bacterial cells decreased by 75% in the presence of 1% (v/v) BMIMPF6 and by about 90% with 1% (v/v) EtPyBF4 or EtPyCF3COO, in comparison to the control without ILs. The diminished biosorption may be attributed to the membrane damages induced by EtPyBF4 and EtPyCF3COO, which can be visualized by Transmission Electron Microscope (TEM) analysis. Energy-dispersive X-ray spectroscopy (EDS) analysis revealed the accumulation of uranium inside peripheral membrane of the cells exposed to uranium alone or with BMIMPF6, while little or no accumulation was observed in the presence of EtPyBF4 and EtPyCF3COO. These results imply that potential toxicity of ILs towards microorganisms is a particularly important issue in limiting its biotechnological applications.

    View details for DOI 10.1016/j.jhazmat.2013.11.003

    View details for Web of Science ID 000331021200030

    View details for PubMedID 24316798

  • C-2-symmetric N,N'-bis(terpenyl)ethylenediamines-synthesis and application in the enantioselective nitroaldol reaction RSC ADVANCES Malhotra, S. V., Brown, H. C. 2014; 4 (27): 14264-14269

    View details for DOI 10.1039/c4ra00193a

    View details for Web of Science ID 000333205200064

  • Synthesis of and Biological Study of 7-Benzyl-3-aminobenzimidazo[3,2- a]quinolinium Chloride (ABQ-48: NSC D-763307) and 7-benzyl-3- nitrobenzimidazo[3,2-a]quinolinium Chloride (NBQ 48: NSC D-763303) Current Bioactive Compounds Cox, O., Velez, C., Kumar, V., Malhotra, S. V., Rivera, L. A., Hernandez, W. J., Martinez, J. R., Cordero, M., Zayas, B. 2014; 10 (4)
  • Anticancer activity of 4-aminoquinoline-triazine based molecular hybrids RSC Advances  Manohar, S., Pepe, A., Velez Gerena, C. E., , Malhotra, S. V., Rawat, D. S. 2014; 4 (14)

    View details for DOI 10.1039/c3ra45333b

  • Bioreduction and precipitation of uranium in ionic liquid aqueous solution by Clostridium sp. BIORESOURCE TECHNOLOGY Zhang, C., Dodge, C. J., Malhotra, S. V., Francis, A. J. 2013; 136: 752-756

    Abstract

    The ionic liquids, 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6], N-ethylpyridiniumtrifluoroacetate [EtPy][CF3COO] and N-ethylpyridiniumtetrafluoroborate [EtPy][BF4], affected the reduction and precipitation of uranium by Clostridium sp. to a varying degree. Characterization of uranium association with the ionic liquids showed that uranium formed a monodentate complex with the anion BF4(-) and PF6(-) of [EtPy][BF4] and [BMIM][PF6], respectively; and a bidentate complex with carboxylate of [EtPy][CF3COO]. Bioreduction of U(VI) was influenced by the type of complex formed: monodentate complexes were readily reduced whereas the bidentate complex of U(VI) with [CF3COO] was recalcitrant. [EtPy][BF4] affected the rate and extent of precipitation of the reduced uranium; at higher concentration the reduced U(IV) remained in the solution phase. The results suggest that by tuning the properties of ionic liquids they may be valuable candidates for uranium biotreatment.

    View details for DOI 10.1016/j.biortech.2013.03.085

    View details for Web of Science ID 000319309400105

    View details for PubMedID 23566468

  • Microwave assisted Westphal condensation and its application to synthesis of sempervirine and related compounds TETRAHEDRON LETTERS Rao, T. S., Saha, S., Raolji, G. B., Patro, B., Risbood, P., Difilippantonio, M. J., Tomaszewski, J. E., Malhotra, S. V. 2013; 54 (6): 487-490
  • Mechanism of the Antiproliferative Activity of Some Naphthalene Diimide G-Quadruplex Ligands MOLECULAR PHARMACOLOGY Hampel, S. M., Pepe, A., Greulich-Bode, K. M., Malhotra, S. V., Reszka, A. P., Veith, S., Boukamp, P., Neidle, S. 2013; 83 (2): 470-480

    Abstract

    G-quadruplexes are higher-order nucleic acid structures that can form in G-rich telomeres and promoter regions of oncogenes. Telomeric quadruplex stabilization by small molecules can lead to telomere uncapping, followed by DNA damage response and senescence, as well as chromosomal fusions leading to deregulation of mitosis, followed by apoptosis and downregulation of oncogene expression. We report here on investigations into the mechanism of action of tetra-substituted naphthalene diimide ligands on the basis of cell biologic data together with a National Cancer Institute COMPARE study. We conclude that four principal mechanisms of action are implicated for these compounds: 1) telomere uncapping with subsequent DNA damage response and senescence; 2) inhibition of transcription/translation of oncogenes; 3) genomic instability through telomeric DNA end fusions, resulting in mitotic catastrophe and apoptosis; and 4) induction of chromosomal instability by telomere aggregate formation.

    View details for DOI 10.1124/mol.112.081075

    View details for Web of Science ID 000313743700015

    View details for PubMedID 23188717

  • Novel nitrobenzazolo[3,2-a]quinolinium salts induce cell death through a mechanism involving DNA damage, cell cycle changes, and mitochondrial permeabilization Open Journal of Apoptosis Velez, C., Cox, O., Rosado-Berrios, C. A., Molina, D., Arroyo, L., Carro, S., Filikov, A., Kumar, V., Malhotra, S. V., Cordero, M. 2013; 2 (2): 13-22
  • Synthesis and cytotoxicity evaluation of novel pyrido[3,4-d]pyrimidine derivatives as potential anticancer agents MEDCHEMCOMM Wei, L., Malhotra, S. V. 2012; 3 (10): 1250-1257

    View details for DOI 10.1039/c2md20097j

    View details for Web of Science ID 000310423600007

  • Highly Efficient One Step Synthesis of Primary Amines from B-Chlorodialkylboranes LETTERS IN ORGANIC CHEMISTRY Malhotra, S. V., Brown, H. C. 2012; 9 (6): 383-385
  • Arylalkyl Ketones, Benzophenones, Desoxybenzoins and Chalcones Inhibit TNF-a Induced Expression of ICAM-1: Structure-Activity Analysis ARCHIV DER PHARMAZIE Kumar, S., Reddy, C. S., Kumar, Y., Kumar, A., Singh, B. K., Kumar, V., Malhotra, S., Pandey, M. K., Jain, R., Thimmulappa, R., Sharma, S. K., Prasad, A. K., Biswal, S., Van der Eycken, E., DePass, A. L., Malhotra, S. V., Ghosh, B., Parmar, V. S. 2012; 345 (5): 368-377

    Abstract

    The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule-1 (ICAM-1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for their ICAM-1 inhibitory activities. The most active compound was found to be 79.

    View details for DOI 10.1002/ardp.201100279

    View details for Web of Science ID 000304088100005

    View details for PubMedID 22190402

  • Highly efficient one step synthesis of primary amines from B-chlorodialkylboranes Letters in Organic Chemistry Malhotra, S. V., Brown, H. C. 2012; 9 (6): 383-385
  • Ionic Liquids: Neoteric Solvents for Nucleoside Chemistry CURRENT ORGANIC SYNTHESIS Kumar, V., Parmar, V. S., Malhotra, S. V. 2011; 8 (6): 777-786
  • Synthetic and Application Perspectives of Azapodophyllotoxins: Alternative Scaffolds of Podophyllotoxin CURRENT MEDICINAL CHEMISTRY Kumar, A., Kumar, V., Alegria, A. E., Malhotra, S. V. 2011; 18 (25): 3853-3870

    Abstract

    Podophyllotoxin (1) has been known to possess anti-tumor activity and is still considered an important lead for research and development of antineoplastic agents. Derivatives of podophyllotoxin, namely etoposide (2), etopophos (3) and teniposide (4) have been developed and are currently used in clinic for the treatment of a variety of malignancies. These agents are also used in combination therapies with other drugs. Due to the drug resistance developed by cancer cells as well as side effects associated with the use of these agents in clinic, the search for new effective anticancer analogues of podophyllotoxin remains an intense area of research. The structural complexity of podophyllotoxin, arising from the presence of four stereogenic carbons in ring C has restricted most of the structural activity relationship (SAR) studied by derivatization of the parent natural product rather than by de novo multi-step chemical synthesis. These issues provide strong impetus to a search for analogues of 1 with simplified structures, which can be accessible via short synthetic sequences from simple starting materials. Even if such initial compounds might have diminished cytotoxic potencies compared with the parent cyclolignan, the ease of preparation of carefully designed libraries of analogues would lead to more informative SAR studies and expeditious structure optimization. In this regard, during the last two decades considerable efforts have been made to synthesize aza- analogs of podophyllotoxin, i. e. aza-podophyllotoxins, with hetero atoms at different positions of the podophyllotoxin skeleton, while keeping the basic podophyllotoxin structure. Recently, there have been significant efforts towards the convenient synthesis of aza-analogs of 1. The use of multicomponent reactions (MCRs) and the synergies of ultrasound and microwave irradiations have increased the synthetic speed and variety of azapodophyllotoxins which are and will be available to be tested against a diverse population of carcinomas and other diseases. It has been reported that several aza-podophyllotoxins retain a great fraction of the cytotoxicity associated with the parent lignan. This review focuses on the strategies towards synthesis of various aza-podophyllotoxin analogues and their biological activities.

    View details for Web of Science ID 000294903300004

    View details for PubMedID 21824101

  • Synthesis and Anticancer Activity of 13-Membered Cyclic Enediynes ARCHIV DER PHARMAZIE Sharma, M., Joshi, M. C., Kumar, V., Malhotra, S. V., Rawat, D. S. 2011; 344 (9): 564-571

    Abstract

    We herein describe the synthesis of 15 novel 13-membered cyclic enediyne derivatives using simple and straightforward approach. Representative examples were screened for their anticancer activities on 60 different human tumor cell lines representing various histologies viz. leukemia, melanoma, and cancers of lung, colon, kidney, ovary, breast, prostate, and central nervous system. The enediyne derivatives with halogen substitutions, especially fluorides were found to be active against most of the cell lines. The initial results indicates marginal to good inhibition for the growth of tumor cells for several cell lines, which shows the potential of these class of compound towards anticancer application.

    View details for DOI 10.1002/ardp.201000309

    View details for Web of Science ID 000295293800002

    View details for PubMedID 21887797

  • Synthesis and biological activity evaluation of N-protected isatin derivatives as inhibitors of ICAM-1 expression on human endothelial cells MEDCHEMCOMM Malhotra, S., Balwani, S., Dhawan, A., Singh, B. K., Kumar, S., Thimmulappa, R., Biswal, S., Olsen, C. E., Van der Eycken, E., Prasad, A. K., Ghosh, B., Parmar, V. S. 2011; 2 (8): 743-751

    View details for DOI 10.1039/c0md00262c

    View details for Web of Science ID 000295068100009

  • Synthesis and Reactivity of Unique Heterocyclic Structures en Route to Substituted Diamines ORGANIC LETTERS Olson, D. E., Maruniak, A., Malhotra, S., Trost, B. M., Du Bois, J. 2011; 13 (13): 3336-3339

    Abstract

    Rhodium-catalyzed oxidative cyclization of allylic hydroxylamine-derived sulfamate esters furnishes a novel family of bicyclic aziridines that serve as functional precursors to substituted diamines. Investigations with the N4-Troc form of these heterocycles have led to manifold improvements in reaction performance and scope and have revealed unique differences in the stability and reactivity of such compounds dictated by the choice of N4-protecting group.

    View details for DOI 10.1021/ol2010769

    View details for Web of Science ID 000291920800013

    View details for PubMedID 21618989

  • O-Glycosidation reactions promoted by in situ generated silver N-heterocyclic carbenes in ionic liquids CARBOHYDRATE RESEARCH Talisman, I. J., Kumar, V., Razzaghy, J., Malhotra, S. V. 2011; 346 (7): 883-890

    Abstract

    We herein report O-glycosidation reactions promoted via silver N-heterocyclic carbene complexes formed in situ in ionic liquids. Seven different room temperature ionic liquids were screened for the glycosidation reaction of 4-nitrophenol with tetra-O-acetyl-α-d-galactopyranosyl bromide. Good to excellent yields were obtained using Ag-NHC complexes derived from imidazolium halide salts to promote the glycosidation reaction, whereas yields considered moderate to low were obtained without use of the silver carbene complex. Anion metathesis of the ionic liquids with inexpensive alkylammonium halides also resulted in silver N-heterocyclic carbene formation and subsequent O-glycosidation in the presence of silver carbonate. Effective utility of this methodology has been demonstrated with biologically relevant acceptors (including flavones and steroids) where O-β-glycoside products were obtained selectively in moderate to good yields. We have also demonstrated that the Ag-NHC complex is a superior promoter to traditionally used silver carbonate for the glycosidation of polyphenolic acceptors. The ionic liquids used in the study could be recycled three times without apparent loss in activity.

    View details for DOI 10.1016/j.carres.2011.03.007

    View details for Web of Science ID 000291176400001

    View details for PubMedID 21459367

  • Toxicity of various anions associated with methoxyethyl methyl imidazolium-based ionic liquids on Clostridium sp. CHEMOSPHERE Wang, H., Malhotra, S. V., Francis, A. J. 2011; 82 (11): 1597-1603

    Abstract

    We investigated the effects on the growth of the anaerobic bacterium, Clostridium sp., of the ionic liquid, 1-methoxyethyl-3-methyl imidazolium [MOEMIM](+), derived from imidazolium cation and paired with one of a variety of counter-ions, viz., tetrafluoroborate [BF₄]⁻, hexafluorophosphate [PF₆]⁻(,) trifluoroacetate [CF₃COO]⁻, bis(trifluoromethane)sulfonamide [Tf₂N]⁻, methane sulfonate [OMS], and 1-butyl-3-methyl imidazolium tetrafluoroborate [BMIM][BF₄]. These anions, in association with [MOEMIM](+) lowered the growth rate of the bacterium, showing the following trend: [Tf₂N]⁻ ≧ [PF₆]⁻ > [BF₄]⁻ > [CF₃COO]⁻ > [OMS]⁻. Anions incorporating fluorine were more toxic than those without it, and their toxicity rose with an increase in the number of fluorine atoms. Also, [MOEMIM](+)[BF₄]⁻ was less toxic than [BMIM](+)[BF₄]⁻, probably due to the presence of a methoxyethyl functional group integrated in the cation side chain.

    View details for DOI 10.1016/j.chemosphere.2010.11.049

    View details for Web of Science ID 000288587900012

    View details for PubMedID 21159360

  • Toxicity of imidazolium- and pyridinium-based ionic liquids and the co-metabolic degradation of N-ethylpyridinium tetrafluoroborate CHEMOSPHERE Zhang, C., Malhotra, S. V., Francis, A. J. 2011; 82 (11): 1690-1695

    Abstract

    We examined the effects of the ionic liquids (ILs), 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF₆], N-ethylpyridinium tetrafluoroborate [EtPy][BF₄], and N-ethylpyridinium trifluoroacetate [EtPy][CF₃COO] on Pseudomonas fluorescens, a ubiquitous soil bacterium. In the presence of 0.5- and 1% of [BMIM][PF₆] or [EtPy][CF₃COO] the growth of bacteria was inhibited, whereas exposing them to 1% [EtPy][BF₄] increased the lag period wherein bacteria adapt to growth conditions before continuing to grow. However, at higher concentrations (5% and 10%), no growth was observed. The inhibitory effects were evident by a decrease in the optical density of the culture, a decline in the consumption of the carbon source, citric acid, and a change in the size of the bacterium. At concentrations below 1%, [EtPy][BF₄] was metabolized by P. fluorescens in the presence of citric acid. Oxidation of the side alkyl-chain of [EtPy][BF₄] caused the accumulation of N-hydroxylethylpyridinium and pyridinium as major degradation products.

    View details for DOI 10.1016/j.chemosphere.2010.10.085

    View details for Web of Science ID 000288587900024

    View details for PubMedID 21112067

  • Biological evaluation of imidazolium- and ammonium-based salts as HIV-1 integrase inhibitors MEDCHEMCOMM Maddali, K., Kumar, V., Marchand, C., Pommier, Y., Malhotra, S. V. 2011; 2 (2): 143-150

    View details for DOI 10.1039/c0md00201a

    View details for Web of Science ID 000288297100008

  • Synthetic and application perspectives of azapodophyllotoxins. Alternative scaffolds of podophyllotoxin Current Medicinal Chemistry Kumar, A., Kumar, V., Alegria, A. E., Malhotra, S. V. 2011; 18 (25): 3853-3870
  • Dual role of ionic liquids as phase transfer catalyst and solvent for glycosidation reactions RSC ADVANCES Kumar, V., Talisman, I. J., Bukhari, O., Razzaghy, J., Malhotra, S. V. 2011; 1 (9): 1721-1727

    View details for DOI 10.1039/c1ra00385b

    View details for Web of Science ID 000297561000014

  • Ionic liquids: neoteric solvents for nucleoside chemistry Current Organic Synthesis Kumar, V., Parmar, V. S., Malhotra, S. V. 2011; 8 (6): 777-786Kumar, Vineet; Parmar, Virinder S.; Malhotra, Sanjay V.
  • A copper chelate of thiosemicarbazone NSC 689534 induces oxidative/ER stress and inhibits tumor growth in vitro and in vivo FREE RADICAL BIOLOGY AND MEDICINE Hancock, C. N., Stockwin, L. H., Han, B., Divelbiss, R. D., Jun, J. H., Malhotra, S. V., Hollingshead, M. G., Newton, D. L. 2011; 50 (1): 110-121

    Abstract

    In this study, a Cu(2+) chelate of the novel thiosemicarbazone NSC 689534 was evaluated for in vitro and in vivo anti-cancer activity. Results demonstrated that NSC 689534 activity (low micromolar range) was enhanced four- to fivefold by copper chelation and completely attenuated by iron. Importantly, once formed, the NSC 689534/Cu(2+) complex retained activity in the presence of additional iron or iron-containing biomolecules. NSC 689534/Cu(2+) mediated its effects primarily through the induction of ROS, with depletion of cellular glutathione and protein thiols. Pretreatment of cells with the antioxidant N-acetyl-l-cysteine impaired activity, whereas NSC 689534/Cu(2+) effectively synergized with the glutathione biosynthesis inhibitor buthionine sulfoximine. Microarray analysis of NSC 689534/Cu(2+)-treated cells highlighted activation of pathways involved in oxidative and ER stress/UPR, autophagy, and metal metabolism. Further scrutiny of the role of ER stress and autophagy indicated that NSC 689534/Cu(2+)-induced cell death was ER-stress dependent and autophagy independent. Last, NSC 689534/Cu(2+) was shown to have activity in an HL60 xenograft model. These data suggest that NSC 689534/Cu(2+) is a potent oxidative stress inducer worthy of further preclinical investigation.

    View details for DOI 10.1016/j.freeradbiomed.2010.10.696

    View details for Web of Science ID 000286407700012

    View details for PubMedID 20971185

  • Structural modifications of nucleosides in ionic liquids BIOCHIMIE Kumar, V., Parmar, V. S., Malhotra, S. V. 2010; 92 (9): 1260-1265

    Abstract

    Nucleoside chemistry represents an important research area for drug discovery, as many nucleoside analogs are prominent drugs and have been widely applied for cancer and viral chemotherapy. However, the synthesis of modified nucleosides presents a major challenge, which is further aggravated by poor solubility of these compounds in common organic solvents. Most of the currently available methods for nucleoside modification employ toxic high boiling solvents; require long reaction time and tedious workup methods. As such, there is constant effort to develop process chemistry in alternative medium to limit the use of organic solvents that are hazardous to the environment and can be deleterious to human health. One such approach is to use ionic liquids, which are 'designer materials' with unique and tunable physico-chemical properties. Studies have shown that methodologies using ionic liquids are highly efficient and convenient for the synthesis of nucleoside analogs, as demonstrated by the preparation of pharmaceutically important anti-viral drugs. This article summarizes recent efforts on nucleoside modification using ionic liquids.

    View details for DOI 10.1016/j.biochi.2010.02.019

    View details for Web of Science ID 000281991400023

    View details for PubMedID 20178825

  • A spectroelectrochemical and chemical study on oxidation of 7,8-dihydroxy-4-methylcoumarin (DHMC) and some related compounds in aprotic medium BIOCHIMIE Petrucci, R., Saso, L., Kumar, V., Prasad, A. K., Malhotra, S. V., Parmar, V. S., Marrosu, G. 2010; 92 (9): 1123-1129

    Abstract

    Electrochemical and chemical oxidation of 7,8-hydroxy-4-methylcoumarin (DHMC 1) and 7,8-diacetoxy-4-methylcoumarin (DAMC 4) were studied to investigate the mechanisms occurring in their antioxidant activities in acetonitrile, under electron transfer and H-atom transfer conditions. Electrolysis and chemical reactions were followed on-line by monitoring the UV spectral changes with time. The anodic oxidation of DHMC, studied by cyclic voltammetry and controlled potential electrolysis, occurs via a reversible one-step two-electrons process, yielding the corresponding stable phenoxonium cation. Moreover, the chemical oxidation with an H-atom acceptor also follows a similar path, yielding the stable neutral quinonic product. Intermediates were never evidenced in both cases. Only in the presence of a strong base, an anodic oxidation product mono-electronic was evidenced, likely the DHMC radical anion. However, the anodic oxidation of the acetoxy derivative DAMC occurs at very high potential values, ruling out the possibility that the antioxidant activity observed in vivo might occur via an electron transfer mechanism; no reactions were evidenced with an H-atom acceptor.

    View details for DOI 10.1016/j.biochi.2010.06.008

    View details for Web of Science ID 000281991400006

    View details for PubMedID 20600572

  • Application of Halide Molten Salts as Novel Reaction Media for O-Glycosidic Bond Formation EUROPEAN JOURNAL OF ORGANIC CHEMISTRY Kumar, V., Talisman, I. J., Malhotra, S. V. 2010: 3377-3381
  • Enantioselective biocatalytic reactions on (+/-)-aryl alkyl ketones with native and modified porcine pancreatic lipase BIOCATALYSIS AND BIOTRANSFORMATION Husain, M., Kumar, V., Kumar, R., Shakil, N. A., Sharma, S. K., Prasad, A. K., Olsen, C. E., Gupta, R. K., Malhotra, S. V., Van der Eycken, E., DePass, A. L., Levon, K., Parmar, V. S. 2010; 28 (3): 172-184
  • Enzymatic Synthesis of Dipeptides in Ionic Liquids LETTERS IN ORGANIC CHEMISTRY Malhotra, S. V., Zhang, C., Wang, H. 2010; 7 (2): 168-171
  • A profile of the in vitro anti-tumor activity of imidazolium-based ionic liquids BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Malhotra, S. V., Kumar, V. 2010; 20 (2): 581-585

    Abstract

    The anti-cancer activity and cytotoxicity of imidazolium-based ionic liquids has been determined for the first time via NCI's in vitro 60 human tumor cell lines. The preliminary SAR showed that the chain length of alkyl substitution at N-3 position of imidazole ring plays crucial role towards anti-tumor activity and cytotoxicity of these ionic liquids. The ionic liquids with alkyl substitution of C-12 chain length were found to be effective against all 60 tumor cell lines and show very low cytotoxicity in most of the cases. Further increase in chain length resulted in enhanced growth inhibition of tumor cell lines as well as high cytotoxicity. Interestingly, active compounds 1-dodecyl-3-methylimidazolium chloride (8), 1-dodecyl-3-methylimidazolium tetrafluoroborate (9), 1-hexadecyl-3-methylimidazoium chloride (10), 1-octadecyl-3-methylimidazolium chloride (11), 1-octadecyl-3-methylimidazolium hexafluorophosphate (12), 1-octadecyl-3-methylimidazolium bis(triflic)imide (13) and 1-octadecyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate (14) were highly active against leukemia cell lines, especially compounds 13 and 14 where the cytotoxicity was also very low as given by LC(50) >100microM in all six leukemia cell lines.

    View details for DOI 10.1016/j.bmcl.2009.11.085

    View details for Web of Science ID 000272936000031

    View details for PubMedID 20006501

  • Ionic Liquid Applications: Pharmaceuticals, Therapeutics, and Biotechnology edited by Malhotra, S. V. American Chemical Society. 2010
  • Recent Development of Cyclic Amide (Pyridone/Lactam) Moiety Containing Heterocycles as Protein Kinase Inhibitors CURRENT MEDICINAL CHEMISTRY Wei, L., Malhotra, S. V. 2010; 17 (3): 234-253

    Abstract

    Staurosporine, pyridone 6 and hydroxyfasudil are cyclic amide (pyridone/lactam) moiety containing heterocycles that are discovered/developed as potent protein kinase inhibitors targeting on the ATP (Adenosine-5'-triphosphate) binding pocket. Despite different molecular shapes (pentacycle, tetracycle and bicycle, respectively), they all bind to the residues of the hinge region at ATP binding pocket of protein kinases in a very similar manner: the cyclic amide moiety occupies the adenine region of ATP binding pocket and forms at least two hydrogen bonding interaction with the hinge region via its hydrogen bond acceptor/donor pair. Using a few examples of cyclic amide (pyridone/lactam) moiety containing heterocyclic protein kinase inhibitors, this review discusses their therapeutic application, structural basis of kinase inhibition, as well as their associated syntheses. It is anticipated that the design, synthesis and profiling of the kinase inhibitor-biased library based upon the cyclic amide (pyridone/lactam) moiety containing core scaffolds may significantly enhance the efficiency of high-throughput screenings (HTS), accelerate hit-to-lead process and improve the success rate in the development of protein kinase inhibitors for the treatment of various diseases especially cancer.

    View details for Web of Science ID 000273740400005

    View details for PubMedID 20214566

  • Arylation of Sensitive 1-(Pyrrolidin-1-yl)-diazen-1-ium-diolate in Ionic Liquids SYNTHETIC COMMUNICATIONS Velazquez, C. A., Lynn, G. M., Kumar, V., Keefer, L. K., Malhotra, S. V. 2010; 40 (9): 1322-1332
  • Recent development of cyclic amide (pyridone/lactam) moiety containing heterocycles as protein kinase inhibitors Current Medicinal Chemistry Wei, L., Malhotra, S. V. 2010; 17 (3): 234-253
  • Ionic Liquids as Pharmaceutical Salts: A Historical Perspective 236th National Meeting of the American-Chemical-Society Kumar, V., Malhotra, S. V. AMER CHEMICAL SOC. 2010: 1–12
  • Antitumor Activity of Ionic Liquids on Human Tumor Cell Lines 236th National Meeting of the American-Chemical-Society Kumar, V., Malhotra, S. V. AMER CHEMICAL SOC. 2010: 91-?
  • Enzymatic synthesis of dipeptides in ionic liquid Letters in Organic Chemistry Malhotra, S. V., Zhang, C., Wang, H. 2010; 7 (2): 168-171
  • Biodegradation of pyridinium-based ionic liquids by an axenic culture of soil Corynebacteria GREEN CHEMISTRY Zhang, C., Wang, H., Malhotra, S. V., Dodge, C. J., Francis, A. J. 2010; 12 (5): 851-858

    View details for DOI 10.1039/b924264c

    View details for Web of Science ID 000277563500018

  • Highly Efficient Method for C-5 Halogenation of Pyrimidine-Based Nucleosides in Ionic Liquids SYNTHESIS-STUTTGART Kumar, V., Yap, J., Muroyama, A., Malhotra, S. V. 2009: 3957-3962
  • Study on the potential anti-cancer activity of phosphonium and ammonium-based ionic liquids BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Kumar, V., Malhotra, S. V. 2009; 19 (16): 4643-4646

    Abstract

    The anti-cancer activity and cytotoxicity of phosphonium and ammonium-based ionic liquids (ILs) have been determined for the first time via NCI's in vitro 60 human tumor cell lines. The preliminary SAR showed that the chain length of alkyl substitution on the cations plays crucial role towards anti-tumor activity and cytotoxicity of these ionic liquids. In general, phosphonium-based ILs were found to be more active and less cytotoxic as compared to ammonium ILs. Cell line data and hollow fiber study has demonstrated the potential of ILs to be developed as therapeutic agent.

    View details for DOI 10.1016/j.bmcl.2009.06.086

    View details for Web of Science ID 000268358800025

    View details for PubMedID 19615902

  • alpha-Pinene-Based New Chiral Ionic Liquids and their Application as Phase Transfer Catalysts in Enantioselective Addition of Diethylzinc to Aldehydes LETTERS IN ORGANIC CHEMISTRY Malhotra, S. V., Wang, Y., Kumar, V. 2009; 6 (3): 264-268
  • α-Pinene-based new chiral ionic liquids and their application as phase transfer catalysts in enantioselective addition of diethylzinc to aldehydes Letters in Organic Chemistry Malhotra, S. V., Wang, Y., Kumar, V. 2009; 6 (3): 264-268
  • IONIC LIQUID MEDIATED SYNTHESIS OF 5-HALOURACIL NUCLEOSIDES: KEY PRECURSORS FOR POTENTIAL ANTIVIRAL DRUGS NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS Kumar, V., Malhotra, S. V. 2009; 28 (9): 821-834

    Abstract

    Synthesis of antiviral 5-halouracil nucleosides, also used as key precursors for the synthesis of other potential antiviral drugs, has been demonstrated using ionic liquids as convenient and efficient reaction medium.

    View details for DOI 10.1080/15257770903170252

    View details for Web of Science ID 000270298400003

    View details for PubMedID 20183621

  • Synthesis of nucleoside-based antiviral drugs in ionic liquids BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Kumar, V., Malhotra, S. V. 2008; 18 (20): 5640-5642

    Abstract

    Nucleoside-based antiviral drugs have been synthesized using imidazolium-based ionic liquids as reaction medium. The ionic liquids were proved to be better solvents for all the nucleoside in terms of solubility and reaction medium as compared to conventional molecular solvents.

    View details for DOI 10.1016/j.bmcl.2008.08.090

    View details for Web of Science ID 000259972800068

    View details for PubMedID 18796352

  • Novel carbohydrate-based chiral ammonium ionic liquids derived from isomannide TETRAHEDRON-ASYMMETRY Kumar, V., Pei, C., Olsen, C. E., Schaffer, S. J., Parmar, V. S., Malhotra, S. V. 2008; 19 (6): 664-671
  • Aminolysis of Epoxides in Ionic Liquid 1-Ethylpyridinium Trifluoroacetate as Green and Efficient Reaction Medium SYNTHETIC COMMUNICATIONS Malhotra, S. V., Andal, R. P., Kumar, V. 2008; 38 (23): 4160-4169
  • FeCl3-catalyzed Pechmann synthesis of coumarins in ionic liquids SYNTHETIC COMMUNICATIONS Kumar, V., Tomar, S., Patel, R., Yousaf, A., Parmar, V. S., Malhotra, S. V. 2008; 38 (15): 2646-2654
  • Antioxidant activity of 4-methylcoumarins Workshop on Chemistry and Biology of Antioxidants Pedersen, J. Z., Oliveira, C., Incerpi, S., Kumar, V., Fiore, A. M., De Vito, P., Prasad, A. K., Malhotra, S. V., Parmar, V. S., Saso, L. PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN. 2007: 1721–28

    Abstract

    Polyphenolic coumarins are known to act as antioxidants in biological systems, but it is difficult to distinguish their antioxidant activity from the many other effects they produce in cells. We have determined the radical scavenging capacity of 22 structurally related natural and synthetic 4-methylcoumarins, by measuring their reaction with radicals, galvinoxyl and 2,2-diphenyl-1-picrylhydrazyl, using electron paramagnetic resonance spectroscopy. Efficient antioxidant activity of 4-methylcoumarins in cells was verified using the DCF fluorescent probe assay for determination of intracellular reactive oxygen species levels. As expected, the o-dihydroxysubstituted coumarins were found to be excellent radical scavengers and better than the m-dihydroxysubstituted or monohydroxysubstituted analogues, but surprisingly the corresponding o-diacetoxy derivatives also turned out to be good scavengers, even in the absence of an esterase. Another unexpected result was that the antioxidant efficiency of 4-methylcoumarins could be modulated by introducing an ethoxycarbonylethyl substituent at the C-3 position; this effect cannot be explained by simple electron donating/withdrawing properties. Coumarin concentrations of 10 microM or less were used in all experiments, corresponding to the levels relevant for therapeutic purposes. Considering that 4-methylcoumarins, in contrast to many other coumarins, are not metabolized to toxic epoxide intermediates, these results indicate promising new strategies for the design of non-toxic antioxidant coumarin-based drugs.

    View details for DOI 10.1211/jpp.59.12.0015

    View details for Web of Science ID 000251849800015

    View details for PubMedID 18053335

  • Asymmetric catalysis in ionic liquids CURRENT ORGANIC SYNTHESIS Malhotra, S. V., Kumar, V., Parmar, V. S. 2007; 4 (4): 370-380
  • Synthesis and applications of novel bis(ammonium) chiral ionic liquids derived from isomannide ORGANIC LETTERS Kumar, V., Olsen, C. E., Schaffer, S. J., Parmar, V. S., Malhotra, S. V. 2007; 9 (20): 3905-3908

    Abstract

    Carbohydrate-based novel bis(ammonium) chiral ionic liquids have been synthesized by following a straightforward protocol using isomannide as the substrate. Their applications in chiral discrimination and optical resolution of racemates have been established.

    View details for DOI 10.1021/ol071390y

    View details for Web of Science ID 000249697800012

    View details for PubMedID 17725360

  • Enhanced solubility and selective benzoylation of nucleosides in novel ionic liquid TETRAHEDRON LETTERS Kumar, V., Parmar, V. S., Malhotra, S. V. 2007; 48 (5): 809-812
  • Ionic Liquids in Organic Synthesis edited by Malhotra, S. V. American Chemical Society. 2007
  • Ionic Liquids as Modifiers for Cationic and Anionic Nanoclays Symposium on Ionic Liquids IV - Not Just Solvents Anymore held at the 231st ACS National Meeting Kim, N. H., Malhotra, S. V., Xanthos, M. AMER CHEMICAL SOC. 2007: 234–246
  • Diels-Alder and Friedel-Crafts Reactions in Pyridinium-Based Ionic Liquids Symposium on Ionic Liquids in Organic Synthesis held at the 228th ACS National Meeting Malhotra, S. V., Xiao, Y. AMER CHEMICAL SOC. 2007: 58–71
  • Asymmetric catalysis in ionic liquids Current Organic Synthesis Malhotra, S. V., Kumar, V., Parmar, V. S. 2007; 4 (4): 370-380
  • Antioxidant activity of 4-methylcoumarins The Journal of pharmacy and pharmacology Pedersen , J. Z., Oliveira , C., Incerpi, S., Kumar, V., Fiore , A., De Vito , P., Prasad , A. K., Malhotra, S. V., Parmar , V. S., Saso , L. 2007; 59 (12): 1721-1728
  • Modification of cationic nanoclays with ionic liquids MICROPOROUS AND MESOPOROUS MATERIALS Kim, N. H., Malhotra, S. V., Xanthos, M. 2006; 96 (1-3): 29-35
  • Synthesis of porous polyurea with room-temperature ionic liquids via interfacial polymerization MACROMOLECULAR RAPID COMMUNICATIONS Zhu, L., Huang, C., Patel, Y. H., Wu, J., Malhotra, S. V. 2006; 27 (16): 1306-1311
  • An experimental and theoretical study of the enantioselective deprotonation of cyclohexene oxide with isopinocampheyl-based chiral lithium amides JOURNAL OF MOLECULAR MODELING Xiao, Y., Jung, D., Gund, T., Malhotra, S. V. 2006; 12 (5): 681-686

    Abstract

    The mechanism of the enantioselective deprotonation of cyclohexene oxide with isopinocampheyl-based chiral lithium amide was studied by quantum chemical calculations. The transition states of eight molecules were fully optimized at the ab initio HF/3-21G and density functional B3LYP/3-21G levels with Gaussian 98. The activation energies were calculated at the B3LYP/6-31+G(3df,2p)//B3LYP/3-21G level. We found the theoretical evaluation to be consistent with the experimental data. At the best case, an enantiomeric excess of up to 95% for (R)-2-scyclohexen-1-ol was achieved with (-)-N, N-diisopinocampheyl lithium amide.

    View details for DOI 10.1007/s00894-006-0114-2

    View details for Web of Science ID 000239248300020

    View details for PubMedID 16705421

  • Application of chiral ionic liquids in the copper catalyzed enantioselective 1,4-addition of diethylzinc to enones TETRAHEDRON-ASYMMETRY Malhotra, S. V., Wang, Y. 2006; 17 (7): 1032-1035
  • Asymmetric reduction of aromatic ketones in pyridinium-based ionic liquids TETRAHEDRON-ASYMMETRY Xiao, Y., Malhotra, S. V. 2006; 17 (7): 1062-1065
  • Enantioselective Friedel-Crafts reactions of aromatic amines with ethyl glyoxylate in pyridinium-based ionic liquids AUSTRALIAN JOURNAL OF CHEMISTRY Malhotra, S. V., Xiao, Y. 2006; 59 (7): 468-472

    View details for DOI 10.1071/CH06221

    View details for Web of Science ID 000239914500008

  • Increased paraoxon detection by acetylcholinesterase inactivation with ionic liquid additives TALANTA Zhang, C. D., Malhotra, S. V. 2005; 67 (3): 560-563

    Abstract

    This is the first study using ionic liquids (ILs) as additive in the aqueous solvent medium for detection of paraoxon by acetylcholinesterase inhibition method. A systematic comparison of various ILs with organic solvents has been made. The aqueous buffer solution containing ionic liquid ethylpyridinium hexafluorophosphate [EtPy](+)[PF(6)](-) has been found to give the best results. The inhibition kinetic follows the first order model. Ionic liquids modified aqueous solutions show the potential to provide a promising and effective medium in detection of paraoxon with acetylcholinesterase.

    View details for DOI 10.1016/j.talanta.2005.03.037

    View details for Web of Science ID 000231936400021

    View details for PubMedID 18970206

  • Friedel-Crafts acylation reactions in pyridinium based ionic liquids JOURNAL OF ORGANOMETALLIC CHEMISTRY Xiao, Y., Malhotra, S. V. 2005; 690 (15): 3609-3613
  • 'Green' methodology for efficient and selective benzoylation of nucleosides using benzoyl cyanide in an ionic liquid BIOORGANIC & MEDICINAL CHEMISTRY Prasad, A. K., Kumar, V., Malhotra, S., Ravikumar, V. T., Sanghvi, Y. S., Parmar, V. S. 2005; 13 (14): 4467-4472

    Abstract

    Benzoyl cyanide in the ionic liquid 1-methoxyethyl-3-methylimidazolium methanesulfonate has been employed as a 'green' alternative and mild reaction condition protocol to conventional pyridine-benzoyl chloride system for efficient and selective benzoylation of nucleosides (of both the ribo- and deoxyribo-series) at ambient temperatures. The use of benzoyl cyanide-ionic liquid combination has been successfully extended for highly efficient benzoylation of phenols, aromatic amines, benzyl alcohol, aliphatic diols, 3-aminophenol and 2-aminobenzylalcohol, which indicates the versatility of this benzoylating system.

    View details for DOI 10.1016/j.bmc.2005.04.038

    View details for Web of Science ID 000230151200013

    View details for PubMedID 15921912

  • Electrochemical nitration of single-wall carbon nanotubes CHEMICAL PHYSICS LETTERS Wang, Y. B., Malhotra, S. V., Owens, F. J., Iqbal, Z. 2005; 407 (1-3): 68-72
  • Friedel-Crafts alkylation reactions in pyridinium-based ionic liquids JOURNAL OF MOLECULAR CATALYSIS A-CHEMICAL Xiao, Y., Malhotra, S. V. 2005; 230 (1-2): 129-133
  • Functionalization of carbon nanotubes with amines and enzymes CHEMICAL PHYSICS LETTERS Wang, Y. B., Iqbal, Z., Malhotra, S. V. 2005; 402 (1-3): 96-101
  • Ionic liquids: Highly effective medium for enantiopure amino acids via enzymatic resolution Symposium on Ionic Liquids - Fundamentals, Progress, Challenges and Opportunities held at the 226th American-Chemical-Society National Meeting Malhotra, S. V., Zhao, H. AMER CHEMICAL SOC. 2005: 111–123
  • Enantioseparation of the esters of alpha-N-acetyl amino acids by lipase in ionic liquid 16th International Symposium on Chiral Discrimination Malhotra, S. V., Zhao, H. WILEY-LISS. 2005: S240–S242

    Abstract

    Chiral alpha-amino acids have been obtained via enzymatic resolution in ionic liquid medium. The acetyl esters of a series of amino acids were separated by enzyme porcine pancreas lipase (PPL) in an aqueous solution of N-ethyl pyridinium trifluoroacetate, [EtPy]+ [CF3OO]-. A comparative study with organic solvent acetonitrile shows that the ionic liquids provide a better medium for enzymatic resolution.

    View details for DOI 10.1002/chir.20132

    View details for Web of Science ID 000230320200031

    View details for PubMedID 15962281

  • Enzymatic degradation of polyurethane-based coatings Annual Technical Conference - Society of Plastics Engineers Malhotra, S. V., Xanthos, M. Society of Plastics Engineers. 2005: 2310–2314
  • Friedel-Crafts acylation reactions in pyridinium based ionic liquids Journal of Organometallic Chemistry Xiao, Y., Malhotra, S. V. 2005; 690 (15): 3609-3613
  • Diels-Alder reactions in pyridinium based ionic liquids TETRAHEDRON LETTERS Xiao, Y., Malhotra, S. V. 2004; 45 (45): 8339-8342
  • Methodologies in Asymmetric Catalysis edited by Malhotra, S. V. American Chemical Society. 2004
  • Nanoscale energetics with carbon nanotubes Symposium on Synthesis, Characterization and Properties of Energetic/Reactive Nanomaterials held at the 2003 MRS Fall Meeting Wang, Y. B., Malhotra, S., Iqbal, Z. MATERIALS RESEARCH SOCIETY. 2004: 351–359
  • Preparation and characterization of three room-temperature ionic liquids PHYSICS AND CHEMISTRY OF LIQUIDS Zhao, H., Malhotra, S. V., Luo, R. G. 2003; 41 (5): 487-492
  • Enantioselective addition of diethylzinc to aldehydes catalyzed by a beta-amino alcohol derived from (+)-3-carene TETRAHEDRON-ASYMMETRY Joshi, S. N., Malhotra, S. V. 2003; 14 (13): 1763-1766
  • Lithium diisopinocampheylamide: a new and highly effective chiral catalyst in the enantioselective deprotonation of meso-epoxides TETRAHEDRON-ASYMMETRY Malhotra, S. V. 2003; 14 (6): 645-647
  • Polymer-supported catalyst for the enantioselective addition of diethylzinc to aldehydes Catalysis of Organic Reactions Malhotra, S. V., Lee, J., Pallerla, M. 2003: 13–19
  • Kinetic Study on the Enzymatic Resolution of Homophenylalanine Ester Using Ionic Liquids Biotechnology Progress Zhao, H., Luo , R. G., Malhotra, S. V. 2003; 19 (3): 1016-1018

    View details for DOI 10.1021/bp025721b

  • Esterification of amino acids by using ionic liquid as a green catalyst Catalysis of Organic Reactions Zhao, H., Malhotra, S. V. 2003: 667–672
  • Enzymatic resolution of amino acid esters using ionic liquid N-ethyl pyridinium trifluoroacetate BIOTECHNOLOGY LETTERS Zhao, H., Malhotra, S. V. 2002; 24 (15): 1257-1260
  • Enzymatic resolution of amino acid esters using ionic liquid N-ethyl pyridinium trifluoroacetate Biotechnology Letters Zhao, H., Malhotra, S. V. 2002; 24 (15): 1257-1259
  • Concise synthesis and enzymatic resolution of L-(+)-homophenylalanine hydrochloride ENANTIOMER Zhao, H., Luo, R. G., Wei, D., Malhotra, S. V. 2002; 7 (1): 1-3

    Abstract

    The N-acetyl-homophenylalanine ethyl ester was synthesized by a simple three-step-reaction strategy. L-(+)-homophenylalanine hydrochloride with 98% ee was obtained through a kinetic resolution process using industrial enzyme alcalase. Compared with other methods, this strategy has the advantage of economical and simple procedure giving high product optical purity.

    View details for Web of Science ID 000175759900001

    View details for PubMedID 12043941

  • Concise synthesis and enzymatic resolution of L-(+)-homophenylalanine hydrochloride Enantiomer Zhao, H., Robert, L. G., Wei, D., Malhotra, S. V. 2002; 7 (1): 1-3

    View details for DOI 10.1080/10242430210706

  • Applications of ionic liquids in organic synthesis Aldrichimica Acta Zhao, H., Malhotra, S. V. 2002; 35 (3): 75-83
  • Chiral synthesis and enzymatic resolution of (S)-(-)piperazine-2-carboxylic acid using enzyme alcalase ENANTIOMER Wu, G. S., Zhao, H., Luo, R. G., Wei, D., Malhotra, S. V. 2001; 6 (6): 343-345

    Abstract

    Enantiomerically pure (S)-piperazine-2-carboxylic acid was synthesized by kinetic resolution of methyl-4-(tert-butyroxycarbonyl)-piperazine-2-carboxylate using a low cost enzyme alcalase.

    View details for Web of Science ID 000174893000005

    View details for PubMedID 11958341

  • Highly effective catalytic enantioselective deprotonation of meso-epoxides with isopinocampheyl based chiral lithium amides Catalysis of Organic Reactions Malhotra, S. V. 2001: 415–424
  • Chiral synthesis and enzymatic resolution of (S)-(-)piperazine-2-carboxylic acid using enzyme alcalase Enantiomer Wu, G., Zhao, H., Luo, R. G., Wei, D., Malhotra, S. V. 2001; 6 (6): 343-345
  • Rate enhancing effect of hydrogen chloride and methanesulfonic acid on the intramolecular asymmetric reduction of o-aminoaceto- and -benzophenones with diisopinocampheylborane 29th ACS Great Lakes Regional Meeting Ramachandran, P. V., Malhotra, S. V., BROWN, H. C. PERGAMON-ELSEVIER SCIENCE LTD. 1997: 957–60
  • Rate enhancing effect of hydrogen chloride and methanesulfonic acid on the intramolecular asymmetric reduction of o-aminoacetophenones and o-aminobenzophenones with diisopinocampheylborane Tetrahedron Letters Ramachandran, P., Malhotra, S. V., Brown, H. C. 1997; 38 (6): 957-960
  • Organoboranes for synthesis. 17. Generality of hydroboration-amination for the conversion of terpenes into enantiomerically pure terpenylamines. Their utility for gas chromatographic analysis of chiral carboxylic acids Tetrahedron: Asymmetry Brown, H. C., Malhotra, S. V., Ramachandran, P. 1996; 7 (12): 3527-3534
  • The support effect on the dispersed metal catalyzed allylic substitution reaction Malhotra, S. V., Augustine, R. L. 1995: 553–556
  • Heterogeneous catalysis in organic synthesis Augustine, R. L., Doyle, L. K., Malhotra, S., Posner, L. S., O'Leary, S., Roberto, S. A., Tanielyan, S. K. 1995: 81–90