Open AccessDesign, Synthesis, Molecular Docking and in vitro Evaluation of N-(4-Methoxyphenylsulfonyl)pyrrolidine-2-carboxylic Acid Analogues as Antiangiogenic and Anticancer Agents on Multiple Myeloma
Author(s) -
Ghosh Avijit,
Abhijit Saha,
Khabiruddin Sarker,
Savita Mishra,
Subrata Sen
Publication year - 2020
Publication title -
asian journal of chemistry/asian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.145
H-Index - 34
eISSN - 0975-427X
pISSN - 0970-7077
DOI - 10.14233/ajchem.2020.22957
Subject(s) - chemistry , mtt assay , cytotoxicity , docking (animal) , stereochemistry , pyrrolidine , in vitro , trypan blue , metabolite , vero cell , biochemistry , pharmacology , biology , medicine , nursing
A series of N-(4-methoxyphenylsulfonyl)pyrrolidine-2-carboxylic acid analogs were designed asbioisosteres 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) byMTS 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 epithelialcells. 2b, 2d, 2i and 2k were found to have primary antiangiogenic activity along with low cytotoxicityon normal vero cells in MTT assay indicating selective cytotoxicity towards highly angiogenic multiplemyeloma. Antiproliferative assay of compounds 2b, 2d, 2i and 2k on HUVECs was carried out usingthe dye exclusion method with trypan blue. Molecular docking study of compound 2b calculated thebinding energy -89.78 kcal/mol and displayed five hydrogen bonds with critical amino acid residues.The compounds are potential candidate drugs for advanced investigations.