Synthesis, Cytotoxicity and Molecular Docking Studies of Chalcone Incorporated 1,2,3-Triazol-1,3,5-Triazin-Quinazoline as Anti-Cancer Agents

Abstract

Chalcone derived 1,2,3-Triazol-1,3,5-Triazin-Quinazoline acts as an anti-cancer agent. It has widespread applications in the medicinal field. We have designed and prepared a novel series of different substituted chalcone derivatives of 1,2,3-triazol-1,3,5-triazin-quinazoline (13a-j). Their chemical structures of chalcone derivatives were further confirmed by spectroscopic techniques (Mass, 1H and 13C NMR). Further, these compounds (13a-j) were screened for their cytotoxic profiles against four different human cancerous cell lines such as PC3 (prostate cancer), A549 (lung cancer), MCF-7 (breast cancer), and DU-145 (prostate cancer) using MTT assay, etoposide acts as a positive control and the cytotoxicity profiles were expressed in IC50 µM values. All the synthesized compounds exhibited good to moderate cytotoxicity activities. Out of all the compounds, specifically 13a compound exhibits good cytotoxicity values in four different cell lines with IC50 values of 0.0071 µM, 0.0094 µM, 0.0083 µM and 0.086 µM respectively. We conclude that 13a displayed good anti-cancerous activity among all the compounds (13b-j). In order to predict the binding interactions between the active site of the tubulin complexed with colchicine as a reference ligand, molecular docking was performed between the compound 13a, into the crystal structure of the tubulin complex with PDB ID: 1SA0 using Maestro 8.5 (Schrodingers LLC, installed in RHEL 5.0 platform. Maestro 10.1). The molecule 13a showed strong interactions due to H bonding, pi- pi interaction and hydrophobic interactions with active site amino acids. With these results, we conclusively validated the selected structural analogues can act as potential anti-cancerous agents.