In Silico and in Vitro Evaluation of (1H-indol-3-ylmethylene)-pyridin-3-yl-amine as a Potent Inhibitor for VEGFR2, EGFR and Progesterone Receptors

Abstract

Carcinomas arising in epithelial tissue, make up 80-90% of all cancer cases among which non-small cell lung cancer (NSCLC) and breast cancer are most commonly diagnosed. In this study, we propose (1H-indol-3-ylmethylene)-pyridin-3-yl-amine (1HIPA) as potential inhibitor for lung and breast cancer. The multi-targeted molecular docking was performed. The inhibitory potential of 1HIPA against lung cancer was evaluated on target proteins VEGFR2 (6XVK), EGFRK (1M17), EGFR/WT (2J6M) & EGFR/T790M (5XGM) and obtained binding affinities were -9.1, -7.6, -7.3, and -6.1 kcal/mol respectively. The binding affinities of 1HIPA against breast cancer target progesterone (PR) with PDBs 1A28 and 4OAR were -8.1 and -7.4 kcal/mol respectively. These results indicate moderate binding affinities of 1HIPA toward both lung and breast cancer targets. Density Functional Theory (DFT) was employed to optimize the geometry of 1HIPA. The optimized structure was then used as the ligand in molecular docking studies and subsequently in the calculation of electronic properties and reactivity descriptors. Ligand (1HIPA) was screened for its anticancer in-vitro activity against Calu-3 and MCF-7 cell lines and obtained inhibitory concentration (IC50) values were 285.99 μg/ml and 491.26 μg/ml respectively. The bioavailability and toxicity profiles were also assessed. The outcomes affirm anti-lung and anti-breast cancer potential of 1HIPA.