New quinazolinone-1,2,4-triazole analogues: Synthesis, anticancer evaluation, molecular docking, and in silico ADMET prediction

Abstract

A novel series of 1,2,4-triazole linked quinazolinone derivatives were created and produced as possible anticancer drugs. The structures of all the compounds were characterized by IR, ¹H NMR, ¹³C NMR, and Mass spectrometric techniques. The anticancer activity of all the prepared derivatives was evaluated against three human cancer cell lines: A549 (Lung cancer), MCF–7 and MDA-MB-231 (Breast cancer) by employing of MTT assay method. Doxorubicin used as reference compound and all the derivatives showed exceptional to moderate activity. The novel scaffolds had IC₅₀ values of ranging from 7.30 ± 1.4 µM to 33.44 ± 1.4 µM while the positive control (DXN) exhibited 8.45 ± 1.9 µM to 13.48 ± 0.8 µM respectively. It was shown that the recently created 1,2,4-triazole hybrids connected with substituted quinazolinone exhibited a considerable percentage of inhibition as anticancer drugs. Additionally, to link the in vitro biological activity data evaluated on three human cancer cell lines, the most active synthesized compounds were studied by molecular docking simulation studies with estrogen receptor alpha enzymatic mutation in breast cancer cell (PDB: 7KBS). The newly synthesized conjugates' docking scores ranged from –8.30 kcal/mol to –8.78 kcal/mol, and interacting residues with His-107, Glu-106, Lys-158, Trp-102, Arg-103, Leu-36, Pro-33, Met-66, Ile-95, Val-155, and Gly-151. Further evidence for the in vitro cytotoxicity behavior of the investigated drugs was obtained from in silico predictions, including SwissADME and PkCSM simulations.