PIFA Mediated Synthesis of Bis‐1,2,4‐triazoloquinazolines as Potential Anticancer Agents on MCF‐7 Cancer Cells: Characterization, Molecular Docking, Antiproliferative and ADME Profile

Abstract

A novel series of bis([1,2,4]triazolo)[4,3‐a][4′,3′‐c] quinazolines derivatives 2 a–2 o has been synthesis in good to excellent yields (74–86 %) under mild reaction conditions via bis(trifluoroacetoxy)iodobenzene (PIFA) mediated oxidative‐cyclization of corresponding 2,4‐bis(2‐(E)‐arylidenehydrazinyl) quinazolines 1 a–1 o. Formation of the targeted compounds has been supported using various spectroscopic tools (IR, 1H & 13 C‐NMR) and HRMS analysis. These bis([1,2,4]triazolo)[4,3‐a][4′,3′‐c] quinazolines derivatives were biologically screened for their antiproliferative activities against MCF‐7 cancer cells. Results indicate that among all synthesized derivatives, 3,7‐bis (4‐chlorophenyl) bis([1,2,4]triazolo)[4,3‐a : 4′,3′‐c]quinazoline (2 d) and 3,7‐bis(3‐methoxyphenyl)bis([1,2,4]triazolo)[4,3‐a : 4′,3′‐c]quinazoline (2 j) displayed uppermost cytotoxicity efficacy with GI50 value of 106.30 μM and 108.56 μM respectively. Furthermore, molecular docking studies have been carried out to investigate possible binding modes between active sites of the protein (PDB ID: 3 U6 J) and the target compounds. In addition to these results, ADME (adsorption, distribution, metabolism, excretion) analysis has also been carried out to study the pharmacokinetic properties of the targeted compounds.