Identification of novel inhibitors of signal transducer and activator of transcription 3 over signal transducer and activator of transcription 1 for the treatment of breast cancer by in-silico and in-vitro approach

Abstract

Abstract In the present study, we have modelled signal transducer and activator of transcription (STAT) 3 and STAT1 proteins using SWISS-MODEL server and refined by molecular dynamic simulations using GROMACS 5.1.2 software for 30 ns. Later, refined protein structures were docked against 29,388 ligands by employing virtual screening workflow and selected 6 novel inhibitors with a better binding affinity towards STAT3over STAT1. Further, density functional theory calculations were carried out to estimate the gap between highest occupied molecular orbital and the lowest unoccupied molecular orbital. In addition, the molecular stability of all the selected protein-ligand complexes were evaluated using GROMACS 5.1.2 software for 30 ns. From this, ligands 5245 and 68740 were chosen for in-vitro studies to screen their anticancer applications and observed potent anti-cancer activities against breast cancer cell lines MCF7 and MDA-MB-231in a dose- and time-dependent manner.