AUTHOR=Oduselu Gbolahan O. , Aderohunmu Damilola V. , Ajani Olayinka O. , Elebiju Oluwadunni F. , Ogunnupebi Temitope A. , Adebiyi Ezekiel 

TITLE=Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs

JOURNAL=Frontiers in Chemistry

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2023.1264824

DOI=10.3389/fchem.2023.1264824

ISSN=2296-2646

ABSTRACT=<p><bold>Introduction:</bold> Quinazolin-4(3<italic>H</italic>)-one derivatives have attracted considerable attention in the pharmacological profiling of therapeutic drug targets. The present article reveals the development of arylidene-based quinazolin-4(3<italic>H</italic>)-one motifs as potential antimicrobial drug candidates.</p><p><bold>Methods:</bold> The synthetic pathway was initiated through thermal cyclization of acetic anhydride on anthranilic acid to produce 2-methyl-4H-3,1-benzoxazan-4-one 1, which (upon condensation with hydrazine hydrate) gave 3-amino-2-methylquinazolin-4(3<italic>H</italic>)-one 2. The reaction of intermediate 2 at its amino side arm with various benzaldehyde derivatives furnished the final products, in the form of substituted benzylidene-based quinazolin-4(3<italic>H</italic>)-one motifs 3a–l, and with thiophene-2-carbaldehyde to afford 3 m. The purified targeted products 3a–m were effectively characterized for structural authentication using physicochemical parameters, microanalytical data, and spectroscopic methods, including IR, UV, and <sup>1</sup>H- and <sup>13</sup>C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3<italic>H</italic>)-one motifs 3a–m were screened for both <italic>in silico</italic> and <italic>in vitro</italic> antimicrobial properties against selected bacteria and fungi. The in silico studies carried out consisted of predicted ADMET screening, molecular docking, and molecular dynamics (MD) simulation studies. Furthermore, <italic>in vitro</italic> experimental validation was performed using the agar diffusion method, and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole, respectively.</p><p><bold>Results and discussion:</bold> Most of the compounds possessed good binding affinities according to the molecular docking studies, while MD simulation revealed their levels of structural stability in the protein–ligand complexes. 2-methyl-3-((thiophen-2-ylmethylene)amino) quinazolin-4(3<italic>H</italic>)-one 3 m emerged as both the most active antibacterial agent (with an minimum inhibitory concentration (MIC) value of 1.95 μg/mL) against Staphylococcus aureus and the most active antifungal agent (with an MIC value of 3.90 μg/mL) against <italic>Candida albicans</italic>, <italic>Aspergillus niger</italic>, and <italic>Rhizopus nigricans</italic>.</p>