Amna earned her Bachelor of Science degree in chemistry and molecular biology from Montclair State University in 2015, where she also worked as a research assistant in the laboratory of Dr. David P. Rotella for 4-years. She pursued a PhD degree in Medicinal Chemistry at the University of Mississippi under the mentorship of Dr. David A. Colby, specializing in fluorine chemistry and organic synthesis. She conducted research on the interface of drug discovery, method development, and synthesis of fluorinated therapeutic for various diagnosis, such as cancer and drug addiction, and neurodegenerative disorders. She developed a method to efficiently synthesize Morpholine 3,3,3-trifluoropropanamide and commercialized this reagent with MilliporeSigma (911933) in 2020. Also, she developed an efficient synthetic reaction to introduce methylene to L-γ-glutamine, which led to the successful synthesis of L-γ-methyleneglutamine that were tested for anticancer activity. Furthermore, she led the method development of fluortrifluoromethyl- and fluoropentafluorosulfanyl-containing methylene in the search of new highly fluorinated therapeutics. Currently, she is a postdoctoral scholar in the Shamloo Laboratory at Stanford Medicine. She works with Professor Shamloo on projects to develop novel therapeutics to treat drug addiction and neurodegenerative diseases.
Bachelor of Science, Montclair State University, Chemistry and Molecular Biology (2015)
Doctor of Philosophy, University of Mississippi, Pharmaceutical Sciences, emphasis in Medicinal Chemistry (2020)
Mehrdad Shamloo, Postdoctoral Faculty Sponsor
David A. Colby and Amna Adam. "United States Patent 62/875,464 Synthesis of β-Fluoro-α,β-Unsaturated Amides (Provisional)", Jul 17, 2019
An efficient synthetic route to l-gamma-methyleneglutamine and its amide derivatives, and their selective anticancer activity
2021; 11 (13): 7115-7128
In cancer cells, glutaminolysis is the primary source of biosynthetic precursors, fueling the TCA cycle with glutamine-derived α-ketoglutarate. The enhanced production of α-ketoglutarate is critical to cancer cells as it provides carbons for the TCA cycle to produce glutathione, fatty acids, and nucleotides, and contributes nitrogens to produce hexosamines, nucleotides, and many nonessential amino acids. Efforts to inhibit glutamine metabolism in cancer using amino acid analogs have been extensive. l-γ-Methyleneglutamine was shown to be of considerable biochemical importance, playing a major role in nitrogen transport in Arachis and Amorpha plants. Herein we report for the first time an efficient synthetic route to l-γ-methyleneglutamine and its amide derivatives. Many of these l-γ-methyleneglutamic acid amides were shown to be as efficacious as tamoxifen or olaparib at arresting cell growth among MCF-7 (ER+/PR+/HER2-), and SK-BR-3 (ER-/PR-/HER2+) breast cancer cells at 24 or 72 h of treatment. Several of these compounds exerted similar efficacy to olaparib at arresting cell growth among triple-negative MDA-MB-231 breast cancer cells by 72 h of treatment. None of the compounds inhibited cell growth in benign MCF-10A breast cells. Overall, N-phenyl amides and N-benzyl amides, such as 3, 5, 9, and 10, arrested the growth of all three (MCF-7, SK-BR-3, and MDA-MB-231) cell lines for 72 h and were devoid of cytotoxicity on MCF-10A control cells; N-benzyl amides with an electron withdrawing group at the para position, such as 5 and 6, inhibited the growth of triple-negative MDA-MB-231 cells commensurate to olaparib. These compounds hold promise as novel therapeutics for the treatment of multiple breast cancer subtypes.
View details for DOI 10.1039/d0ra08249j
View details for Web of Science ID 000619136600001
View details for PubMedID 33777357
View details for PubMedCentralID PMC7968037
Synthesis of beta-Fluoro-alpha,beta-Unsaturated Amides from the Fragmentation of Morpholine 3,3,3-Trifluoropropanamide by Grignard Reagents
2020; 22 (7): 2630-2633
Fluoroalkenes serve as bioisosteres to peptide bonds and are resistant to hydrolytic enzymes in vivo. Currently, α-fluoro-α,β-unsaturated carbonyl compounds are readily accessible via general synthetic methods; however, β-fluoro-α,β-unsaturated carbonyl groups are more challenging to construct. To address this need, we have designed a reagent, morpholine 3,3,3-trifluoropropanamide, that creates (E)-β-fluoro-α,β-unsaturated amides upon the addition of many commonly used Grignard reagents. Reactions with this reagent enable a high level of stereocontrol in the fluoroalkene product.
View details for DOI 10.1021/acs.orglett.0c00599
View details for Web of Science ID 000526335800026
View details for PubMedID 32181669
View details for PubMedCentralID PMC7465497
Controlling the Cleavage of Carbon-Carbon Bonds To Generate alpha,alpha-Difluorobenzyl Carbanions for the Construction of Difluoromethylbenzenes
JOURNAL OF ORGANIC CHEMISTRY
2019; 84 (18): 11665-11675
Controlling the cleavage of carbon-carbon bonds during a chemical reaction is a substantial challenge; however, synthetic methods that accomplish this objective produce valuable and often unexplored reactivity. We have designed a mild process to generate α,α-difluorobenzyl carbanions in the presence of potassium carbonate by exploiting the cleavage of C-C bonds during the release of trifluoroacetate. The initiating reagent is potassium carbonate, which represents an improvement over existing protocols that require a strong base. Fragmentation studies across substituted arenes and heteroarenes were conducted along with computational analyses to elucidate reactivity trends. Furthermore, the mildly generated α,α-difluorobenzyl carbanions from electron-deficient aromatics and heteroaromatic rings can react with aldehydes to create derivatives of difluoromethylbenzenes, which are valuable synthetic targets.
View details for DOI 10.1021/acs.joc.9b01595
View details for Web of Science ID 000487576900027
View details for PubMedID 31449418
View details for PubMedCentralID PMC8262649
Structure-activity studies of (-)-epigallocatechin gallate derivatives as HCV entry inhibitors
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
2014; 24 (17): 4162-4165
Preventing viral entry into cells is a recognized approach for HIV therapy and has attracted attention for use against the hepatitis C virus (HCV). Recent reports described the activity of (-)-epigallocatechin gallate (EGCG) as an inhibitor of HCV entry with modest potency. EGCG is a polyphenolic natural product with a wide range of biological activity and unfavorable pharmaceutical properties. In an attempt to identify more drug-like EGCG derivatives with improved efficacy as HCV entry inhibitors, we initiated structure-activity investigations using semi-synthetic and synthetic EGCG analogs. The data show that there are multiple regions in the EGCG structure that contribute to activity. The gallate ester portion of the molecule appears to be of particular importance as a 3,4-difluoro analog of EGCG enhanced potency. This derivative and other active compounds were shown not to be cytotoxic in Huh-7 cell culture. These data suggest that more potent, non-cytotoxic EGCG analogs can be prepared in an attempt to identify more drug-like candidates to treat HCV infection by this mechanism.
View details for DOI 10.1016/j.bmcl.2014.07.051
View details for Web of Science ID 000341339300017
View details for PubMedID 25103601
Towards the discovery of drug-like epigallocatechin gallate analogs as Hsp90 inhibitors
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
2014; 24 (10): 2263-2266
(-)-Epigallocatechin gallate (EGCG) is the major flavonoid of green tea and has been widely explored for a range of biological activities including anti-infective, anti-inflammatory, anti-cancer, and neuroprotection. Existing structure-activity data for EGCG has been largely limited to exploration of simple ethers and hydroxyl deletion. EGCG has poor drug-like properties because of multiple phenolic hydroxyl moieties and a metabolically labile ester. This work reports a substantial expansion of structure-activity understanding by exploring a range of semi-synthetic and synthetic derivatives with ester replacements and variously substituted aromatic and alicyclic groups containing more drug-like substituents. Structure-activity relationships for these molecules were obtained for Hsp90 inhibition. The results indicate that amide and sulfonamide linkers are suitable ester replacements. Hydroxylated aromatic rings and the cis-stereochemistry in EGCG are not essential for Hsp90 inhibition. Selected analogs in this series are more potent than EGCG in a luciferase refolding assay for Hsp90 activity.
View details for DOI 10.1016/j.bmcl.2014.03.088
View details for Web of Science ID 000335517300007
View details for PubMedID 24745965