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

Autor:	Oduselu GO; Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria., Aderohunmu DV; Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria., Ajani OO; Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria.; Department of Chemistry, Covenant University, Ota, Ogun State, Nigeria., Elebiju OF; Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria.; Department of Chemistry, Covenant University, Ota, Ogun State, Nigeria., Ogunnupebi TA; Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria.; Department of Chemistry, Covenant University, Ota, Ogun State, Nigeria., Adebiyi E; Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, Nigeria.; Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in chemistry [Front Chem] 2023 Sep 25; Vol. 11, pp. 1264824. Date of Electronic Publication: 2023 Sep 25 (Print Publication: 2023).
DOI:	10.3389/fchem.2023.1264824
Abstrakt:	Introduction: Quinazolin-4(3 H )-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 H )-one motifs as potential antimicrobial drug candidates. Methods: 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 H )-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 H )-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 1 H- and 13 C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3 H )-one motifs 3a-m were screened for both in silico and in vitro 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, in vitro experimental validation was performed using the agar diffusion method, and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole, respectively. Results and discussion: 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 H )-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 Candida albicans , Aspergillus niger , and Rhizopus nigricans . Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Oduselu, Aderohunmu, Ajani, Elebiju, Ogunnupebi and Adebiyi.)
Databáze:	MEDLINE
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