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Vol. 32 No. 12 (2020): Vol 32 Issue 12, 2020

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Design, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Methoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma

https://doi.org/10.14233/ajchem.2020.22957
K. Sarker
A.P.C. Ray Memorial Cancer Chemotherapeutic Research Unit, College of Pharmaceutical Sciences, Mohuda, Berhampur-760002, India
A. Ghosh
A.P.C. Ray Memorial Cancer Chemotherapeutic Research Unit, College of Pharmaceutical Sciences, Mohuda, Berhampur-760002, India
S. Mishra
A.P.C. Ray Memorial Cancer Chemotherapeutic Research Unit, College of Pharmaceutical Sciences, Mohuda, Berhampur-760002, India
A. Saha
A.P.C. Ray Memorial Cancer Chemotherapeutic Research Unit, College of Pharmaceutical Sciences, Mohuda, Berhampur-760002, India
S. Sen
A.P.C. Ray Memorial Cancer Chemotherapeutic Research Unit, College of Pharmaceutical Sciences, Mohuda, Berhampur-760002, India

Corresponding Author(s) : S. Sen

prof.dr.subratasen@gmail.com

Asian Journal of Chemistry, Vol. 32 No. 12 (2020): Vol 32 Issue 12, 2020

Abstract

A series of N-(4-methoxyphenylsulfonyl)pyrrolidine-2-carboxylic acid analogs were designed as bioisosteres of a major metabolite of thalidomide, i.e., N-(o-carboxybenzoyl)-D,L-glutamic acid. Compounds 2b, 2d, 2f, 2i and 2k exhibited anticancer activity on multiple myeloma (RPMI 8226) by MTS assay and were tested for primary antiangiogenic activity on HUVEC cell line by MTT assay. Compound 2f was excluded from further study as it was found to be cytotoxic to normal epithelial cells. 2b, 2d, 2i and 2k were found to have primary antiangiogenic activity along with low cytotoxicity on normal vero cells in MTT assay indicating selective cytotoxicity towards highly angiogenic multiple myeloma. Antiproliferative assay of compounds 2b, 2d, 2i and 2k on HUVECs was carried out using the dye exclusion method with trypan blue. Molecular docking study of compound 2b calculated the binding energy -89.78 kcal/mol and displayed five hydrogen bonds with critical amino acid residues. The compounds are potential candidate drugs for advanced investigations.

Keywords

Thalidomide Angiogenesis Multiple myeloma Vero RPMI8226 Molecular docking
Sarker, K., Ghosh, A., Mishra, S., Saha, A., & Sen, S. (2020). Design, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Methoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma. Asian Journal of Chemistry, 32(12), 3079–3086. https://doi.org/10.14233/ajchem.2020.22957
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