Synthesis of 8-methyl-2-phenylquinazolin-4(3H)-ones derived Schiff's bases: Spectroscopic properties, SAR, docking approaches and their anticancer and antimicrobial activity

Abstract

A series of new compounds based on 8-methyl-2-phenyl quinazolinone Schiff's base were synthesized from 3-amino quinazolinone intermediates. These compounds were evaluated for their potential as anticancer and antimicrobial agents through docking analysis. Anticancer evaluation was done against sixty different cancer cell lines. Compounds 7b and 7 h showed strong efficacy against Melanoma (MDA-MB-435 Cell lines) and Non-Small Cell Lung Cancer (NCI-H522), respectively. Compound 7 g was found to be predominantly effective against both breast cancer (HS-578T) and central nervous system cancer (SNB-19). The antimicrobial activity results showed that the newly synthesized compounds 7d and 7j, which contain halogen, exhibited potential inhibiting action against selected bacterial and fungal microorganisms. The SAR study revealed that compounds with EDGs like hydroxyl and meta-substituted chloro group were found to be more potent in anticancer studies; while compounds with EWGs substituted in the para position (7d and 7j) demonstrated higher antimicrobial activity. Moreover, Antimicrobial docking analysis indicated that compounds 7d and 7j have a high affinity towards molecular targets found in both bacteria and fungi, with negative binding energies ranging from -8 to -12.5 kcal/mol. We endorse further evaluation of these compounds in combination with standard antibiotics to potentially increase their synergistic effect.