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.

Automated summary

In this study, a series of new isatin-1,2,4-oxadiazole hybrids were synthesized using a one-pot method and screened for cytotoxicity. Three compounds showed superior activity and demonstrated inhibitory effects in in vitro experiments. Molecular docking and ADMET studies were also performed.