RATIONAL DESIGN, SYNTHESIS AND IN VITRO EVALUATION OF N-(4- ETHOXYPHENYLSULFONYL)-L-GLUTAMIC ACID ANALOGUES AS ANTIANGIOGENIC AND ANTICANCER AGENTS ON MULTIPLE MYELOMA.

We report the rational design, synthesis and evaluation of the anticancer and antiangiogenic activity of the N-(4-ethoxyphenylsulfonyl)-L-glutamic acid analogs on multiple myeloma. From the series, compound 2c, 2f, and 2h exhibit cytotoxic action on human multiple myeloma cell line RPMI8226 with IC50 (μM) value 2.72, 2.24, and 1.81, respectively. These compounds possess the antiangiogenic property and are selectively cytotoxic to cancer cells, as observed from the in vitro study of Human Umbilical Vein endothelial cell (HUVEC) and African green monkey kidney epithelial cell (VERO), respectively. The compounds also have an antiproliferative effect on HUVECs, which was carried out using the dye exclusion method with trypan blue. Vascular endothelial Growth Factor Receptor-2 (VEGFR-2) Tyr-1175 phosphorylation inhibition assay showed compound 2f, and 2h to be the active inhibitors of proangiogenic responses mediated by VEGFR-2. A molecular docking study of 2f with VEGFR-2 showed possible interaction with a binding energy of -74.19 kcal/mol. [ABSTRACT FROM AUTHOR]