DOI: https://doi.org/10.55373/mjchem.v24i3.132

Keywords: Quinazoline; in-vitro activity; molecular Docking; in-silico ADME study

Abstract

A novel series of N-4-(substituted benzylidene)-N-2-(4-chloropyrimidine-2-yl)-6,7- dimethoxyquinazoline-2,4-diamine compounds were designed, synthesized and evaluated for their anti-cancer properties. The structures of the target derivatives were elucidated using spectral techniques like 1H NMR, 13C NMR and mass spectroscopy. All the designed compounds were tested for their probable anti-cancer activity on human colon-rectal cell lines (HT-29 and COLO-205), followed by cell-cycle analysis, apoptosis assays, and enzyme inhibitory assays. VEGFR-2 kinase inhibitory assays and cell cycle analyses were performed to validate the target selectivity of the designed compounds. Among the synthesized derivatives, SM-8 (GI50= 10.64 µM) showed good inhibition activity against HT-29 cell lines. Cellular mechanism studies confirmed that compound SM-8 could induce apoptosis in HT-29 cells in G1 phase, which was concentration-dependent. In order to evaluate the specific interaction with tyrosine kinase, designed scaffolds were subjected to docking, in-silico physicochemical properties and ADME prediction studies. MM/GBSA was performed to calculate the ligand binding free energies.