One‐Pot Synthesis of Isatin‐Pyrazole Hybrids as VEGFR‐2 Inhibitors and Molecular Docking Studies

Abstract

AbstractHerein, we described the synthesis of isatin‐pyrazole hybrids (6 a–o) using Acyl‐Sonogashira coupling reaction and evaluated for their in vitro cytotoxicity against three human cancer cell lines such as A549, PC3 and MCF‐7 by using MTT assay and 5‐fluorouracil as the reference drug. Some of the compounds 6 a, 6 j and 6 n were found to be more active than the standard 5‐fluorouracil against three human cancer cell lines. The in vitro VEGFR‐2 tyrosine kinase inhibitory activity reveals that 6 j has exhibited double inhibitory potency with IC50 value of 16.28±1.21 nM compared to reference drug sorafenib and 6 a and 6 n were also shown more inhibition capacity than the standard. Molecular docking studies of the compounds 6 a, 6 j and 6 n towards human VEGFR2 kinase shown that they have good binding interactions with the target protein with binding energies ranging from −10.30 kcal/mol to −10.80 kcal/mol. Finally, the in silico pharmacokinetic profile (ADMET) of potent compounds 6 a, 6 j and 6 n were also studied, where all of them have followed Lipinski rule, Ghose rule, Veber rule, Egan rule and Muegge rule without any deviation and the compounds 6 a and 6 j have shown lead likeness in medicinal chemistry point of view.