Bio


Accomplished Research Scientist with a rich history (6-8 years) of spearheading cutting-edge research projects. Proficient in synthesizing and analyzing new compounds with therapeuIc potenIal. Experienced in uIlizing both structureand property-based strategies to idenIfy promising drug candidates. Led mulIdisciplinary teams to innovate soluIons, enhanced drug discovery efficiency by integraIng advanced computaIonal techniques. CommiYed to conInuous learning and staying well-informed of the latest trends in medicinal chemistry and drug design.

Academic Appointments


All Publications


  • Novel orexin receptor agonists based on arene- or pyridine-fused 1,3-dihydro-2H-imidazole-2-imines BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Wang, W., Ranjan, A., Zhang, W., Liang, Q., MacMillan, K. S., Chapman, K., Wang, X., Chandrasekaran, P., Williams, N. S., Rosenbaum, D. M., De Brabander, J. K. 2024; 99: 129624

    Abstract

    A structurally novel class of benzo- or pyrido-fused 1,3-dihydro-2H-imidazole-2-imines was designed and evaluated in an inositol phosphate accumulation assay for Gq signaling to measure agonistic activation of the orexin receptor type 2 (OX2R). These compounds were synthesized in 4-9 steps overall from readily available starting materials. Analogs that contain a stereogenic methyl or cyclopropyl substituent at the benzylic center, and a correctly configured alkyl ether, alkoxyalkyl ether, cyanoalkyl ether, or α-hydroxyacetamido substituted homobenzylic sidechain were identified as the most potent activators of OX2R coupled Gq signaling. Our results also indicate that agonistic activity was stereospecific at both the benzylic and homobenzylic stereogenic centra. We identified methoxyethoxy-substituted pyrido-fused dihydroimidazolimine analog 63c containing a stereogenic benzylic methyl group was the most potent agonist, registering a respectable EC50 of 339 nM and a maximal response (Emax) of 96 % in this assay. In vivo pharmacokinetic analysis indicated good brain exposure for several analogs. Our combined results provide important information towards a structurally novel class of orexin receptor agonists distinct from current chemotypes.

    View details for DOI 10.1016/j.bmcl.2024.129624

    View details for Web of Science ID 001171642200001

    View details for PubMedID 38272190

  • Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells Dimapasoc, M., Moran, J. A., Cole, S. W., Ranjan, A., Hourani, R., Kim, J. T., Wender, P. A., Marsden, M. D., Zack, J. A. 2024; 9 (1): 108 - 137

    View details for DOI 10.20411/pai.v9i1.673

  • Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism. Nature communications Li, Z., Amaya, L., Pi, R., Wang, S. K., Ranjan, A., Waymouth, R. M., Blish, C. A., Chang, H. Y., Wender, P. A. 2023; 14 (1): 6983

    Abstract

    The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems.

    View details for DOI 10.1038/s41467-023-42672-x

    View details for PubMedID 37914693

  • Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice. Journal of sleep research Sun, Y., Ranjan, A., Tisdale, R., Ma, S., Park, S., Haire, M., Heu, J., Morairty, S. R., Wang, X., Rosenbaum, D. M., Williams, N. S., De Brabander, J. K., Kilduff, T. S. 2023: e13839

    Abstract

    The sleep disorder narcolepsy, a hypocretin deficiency disorder thought to be due to degeneration of hypothalamic hypocretin/orexin neurons, is currently treated symptomatically. We evaluated the efficacy of two small molecule hypocretin/orexin receptor-2 (HCRTR2) agonists in narcoleptic male orexin/tTA; TetO-DTA mice. TAK-925 (1-10mg/kg, s.c.) and ARN-776 (1-10mg/kg, i.p.) were injected 15min before dark onset in a repeated measures design. EEG, EMG, subcutaneous temperature (Tsc ) and activity were recorded by telemetry; recordings for the first 6 h of the dark period were scored for sleep/wake and cataplexy. At all doses tested, TAK-925 and ARN-776 caused continuous wakefulness and eliminated sleep for the first hour. Both TAK-925 and ARN-776 caused dose-related delays in NREM sleep onset. All doses of TAK-925 and all but the lowest dose of ARN-776 eliminated cataplexy during the first hour after treatment; the anti-cataplectic effect of TAK-925 persisted into the second hour for the highest dose. TAK-925 and ARN-776 also reduced the cumulative amount of cataplexy during the 6 h post-dosing period. The acute increase in wakefulness produced by both HCRTR2 agonists was characterised by increased spectral power in the gamma EEG band. Although neither compound provoked a NREM sleep rebound, both compounds affected NREM EEG during the second hour post-dosing. TAK-925 and ARN-776 also increased gross motor activity, running wheel activity, and Tsc , suggesting that the wake-promoting and sleep-suppressing activities of these compounds could be a consequence of hyperactivity. Nonetheless, the anti-cataplectic activity of TAK-925 and ARN-776 is encouraging for the development of HCRTR2 agonists.

    View details for DOI 10.1111/jsr.13839

    View details for PubMedID 36808670

  • Secreted factors induced by PKC modulators do not indirectly cause HIV latency reversal. Virology Moran, J. A., Ranjan, A., Hourani, R., Kim, J. T., Wender, P. A., Zack, J. A., Marsden, M. D. 2023; 581: 8-14

    Abstract

    HIV can establish a long-lived latent infection in cells harboring integrated non-expressing proviruses. Latency reversing agents (LRAs), including protein kinase C (PKC) modulators, can induce expression of latent HIV, thereby reducing the latent reservoir in animal models. However, PKC modulators such as bryostatin-1 also cause cytokine upregulation in peripheral blood mononuclear cells (PBMCs), including cytokines that might independently reverse HIV latency. To determine whether cytokines induced by PKC modulators contribute to latency reversal, primary human PBMCs were treated with bryostatin-1 or the bryostatin analog SUW133, a superior LRA, and supernatant was collected. As anticipated, LRA-treated cell supernatant contained increased levels of cytokines compared to untreated cell supernatant. However, exposure of latently-infected cells with this supernatant did not result in latency reactivation. These results indicate that PKC modulators do not have significant indirect effects on HIV latency reversal in vitro and thus are targeted in their latency reversing ability.

    View details for DOI 10.1016/j.virol.2023.02.009

    View details for PubMedID 36842270

  • Trimethylene Methane Dianion Equivalent for the Asymmetric Consecutive Allylation of Aldehydes: Applications to Prins-Driven Macrocyclizations for the Synthesis of Bryostatin 1 and Analogues. The Journal of organic chemistry Wender, P. A., Luu-Nguyen, Q. H., Sloane, J. L., Ranjan, A. 2022

    Abstract

    We report a one-step (one-flask) generation and reaction of a bifunctional allylating reagent, a trimethylene methane dianion equivalent, that provides a route for the asymmetric 2-(trimethylsilylmethyl) allylation of aldehydes. The product of the first aldehyde allylation process is then set to engage in a second separate aldehyde allylation, providing an improved Prins macrocyclization strategy both for the scalable synthesis of bryostatin 1 and for the total synthesis of a new potent bryostatin analogue.

    View details for DOI 10.1021/acs.joc.2c02047

    View details for PubMedID 36378802

  • Thiol-Yne Coupling of Propargylamine under Solvent-Free Conditions by Bond Anion Relay Chemistry: An Efficient Synthesis of Thiazolidin-2-ylideneamine EUROPEAN JOURNAL OF ORGANIC CHEMISTRY Ranjan, A., Deore, A. S., Yerande, S. G., Dethe, D. H. 2017; 2017 (28): 4130-4139
  • An asymmetric alkynylation/hydrothiolation cascade: an enantioselective synthesis of thiazolidine-2-imines from imines, acetylenes and isothiocyanates. Chemical communications (Cambridge, England) Ranjan, A., Mandal, A., Yerande, S. G., Dethe, D. H. 2015; 51 (75): 14215-8

    Abstract

    A multicomponent reaction between imines, terminal alkynes, and isothiocyanates in the presence of a catalytic chiral copper-pybox complex proceeds enantioselectively to give enantiopure thiazolidine-2-imines (60-99% ee) via a highly regioselective intramolecular 5-exo-dig hydrothiolation reaction.

    View details for DOI 10.1039/c5cc05549k

    View details for PubMedID 26255639

  • One-Pot Synthesis of 2-Amino-1,3-selenazole via an Intermediary Amidinoselenourea EUROPEAN JOURNAL OF ORGANIC CHEMISTRY Ranjan, A., Yerande, R., Jadhav, M., Yerande, S. G., Dethe, D. H. 2015; 2015 (15): 3230-3234
  • Base-mediated hydroamination of propargylamine: a regioselective intramolecular 5-exo-dig cycloisomerization en route to imidazole-2-thione. Organic letters Ranjan, A., Yerande, R., Wakchaure, P. B., Yerande, S. G., Dethe, D. H. 2014; 16 (21): 5788-91

    Abstract

    An intramolecular transition-metal-free base-mediated hydroamination of propargylamine with isothiocyanates has been achieved. This atom-economical, regioselective intramolecular 5-exo-dig cycloisomerization was utilized for the one-pot synthesis of diversely substituted imidazole-2-thione and spiro-cyclic imidazolidine-2-thione. The reaction goes to completion at room temperature via propargylthiourea and 65-97% isolated yields were obtained.

    View details for DOI 10.1021/ol502871r

    View details for PubMedID 25351666

  • Biomimetic total syntheses of borreverine and flinderole alkaloids. The Journal of organic chemistry Dethe, D. H., Erande, R. D., Ranjan, A. 2013; 78 (20): 10106-20

    Abstract

    Dimeric indole alkaloids represent a structurally unique class of natural products having interesting biological activities. Recently, we reported the first total synthesis of flinderoles B and C, structurally unique and potent antimalarial natural products. Central to the design of the approach and by virtue of a one-pot, acid-catalyzed dimerization reaction, the route also provided total synthesis of the borreverine class of natural products. This full account details the progress of efforts that culminated in the protecting-group-free, six-step total synthesis of all of the flindersia alkaloids: dimethylisoborreverine, isoborreverine, flinderoles A-C, and their analogues. A biomimetic approach featuring a scalable and catalytic formal [3 + 2] cycloaddition and Diels-Alder reaction is outlined in detail. On the basis of the experimental observations, a detailed mechanism has been proposed for the dimerization of tertiary alcohol 28.

    View details for DOI 10.1021/jo4013833

    View details for PubMedID 24044378

  • Enantioselective total syntheses and determination of absolute configuration of marine toxins, oxazinins RSC ADVANCES Dethe, D. H., Ranjan, A. 2013; 3 (45): 23692-23703

    View details for DOI 10.1039/c3ra44631j

    View details for Web of Science ID 000326395800132

  • Asymmetric first total syntheses and assignment of absolute configuration of oxazinin-5, oxazinin-6 and preoxazinin-7. Organic & biomolecular chemistry Dethe, D. H., Ranjan, A., Pardeshi, V. H. 2011; 9 (23): 7990-2

    Abstract

    Asymmetric first total syntheses of the unprecedented toxins oxazinin-5, oxazinin-6 and preoxazinin-7 have been achieved from a common key intermediate 18, derived from a regiocontrolled Sharpless asymmetric aminohydroxylation and oxa-Michael reaction, which in addition to confirming the structure also established the absolute configuration of the natural products. On the way an expeditious synthesis of a metabolite bursatellin was completed in 8 steps.

    View details for DOI 10.1039/c1ob06320k

    View details for PubMedID 21952949

  • Biomimetic total syntheses of flinderoles B and C. Journal of the American Chemical Society Dethe, D. H., Erande, R. D., Ranjan, A. 2011; 133 (9): 2864-7

    Abstract

    A simple and efficient biomimetic synthesis of pyrrolo[1,2-a]indoles using a highly stereo- and regioselective [3 + 2] reaction cascade was developed and then further applied in the first total synthesis of flinderoles B and C, which proceeded in 17.2% yield over the longest linear sequence of 11 steps.

    View details for DOI 10.1021/ja1116974

    View details for PubMedID 21314186