Design, synthesis, anticancer evaluation, and molecular modelling studies of novel tolmetin derivatives as potential VEGFR-2 inhibitors and apoptosis inducers

Novel tolmetin derivatives 5a–f to 8a–c were designed, synthesised, and evaluated for antiproliferative activity by NCI (USA) against a panel of 60 tumour cell lines. The cytotoxic the most active 5b 5c was examined HL-60, HCT-15, UO-31 Compound found be potent derivative lines with IC50 values 10.32 ± 0.55, 6.62 0.35, 7.69 0.41 µM, respectively. Molecular modelling studies towards VEGFR-2 site performed. displayed high inhibitory (IC50 = 0.20 µM). It extremely reduced HUVECs migration potential exhibiting deeply wound healing patterns after 72 h. induced apoptosis in HCT-15 cells (52.72-fold). This evidence supported an increase level apoptotic caspases-3, -8, -9 7.808-, 1.867-, 7.622-fold, arrested cycle G0/G1 phase. Furthermore, ADME showed that compound possessed promising pharmacokinetic properties.