One-pot Synthesis of Some New Isatin-1,2,4-Oxadiazole Hybrids as VEGFR-2 Aiming Anticancer Agents

The one-pot synthesis of some new isatin-1,2,4-oxadiazole hybrids (3 a-n) in moderate to good yields via reaction between 3-((1-methyl-2-oxoindolin-3-ylidene)amino)propane nitrile and several aromatic carboxylic acids using the key reagents like NH2OH.HCl, Et3N and POCl3/DMF was described herein. The synthesized compounds were screened for the cytotoxicity against three human cancer cell lines such as A549, PC3 and DU145. Among them, three compounds (3 d, 3 e and 3 l) were exhibited superior activity than the standard 5-fluorouracil against all the cell lines. In vitro VGEFR-2 tyrosine kinase assay on 3 d, 3 e and 3 l indicates that 3 l has more inhibiting power than the standard sorafenib.Further, in silico studies like molecular docking studies on VEGFRs and ADMET performed to know binding affinity towards VEGFRs and drug likeness properties.