Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs
Introduction: Quinazolin-4(3H)-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(3H)-one motifs as potential antimicrobial drug candidates.Methods: The synthe...
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1264824/full |
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| author | Gbolahan O. Oduselu Damilola V. Aderohunmu Olayinka O. Ajani Olayinka O. Ajani Oluwadunni F. Elebiju Oluwadunni F. Elebiju Temitope A. Ogunnupebi Temitope A. Ogunnupebi Ezekiel Adebiyi Ezekiel Adebiyi |
| author_facet | Gbolahan O. Oduselu Damilola V. Aderohunmu Olayinka O. Ajani Olayinka O. Ajani Oluwadunni F. Elebiju Oluwadunni F. Elebiju Temitope A. Ogunnupebi Temitope A. Ogunnupebi Ezekiel Adebiyi Ezekiel Adebiyi |
| author_sort | Gbolahan O. Oduselu |
| collection | DOAJ |
| description | Introduction: Quinazolin-4(3H)-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(3H)-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(3H)-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(3H)-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 1H- and 13C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3H)-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(3H)-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. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-11T21:52:22Z |
| publishDate | 2023-09-01 |
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| series | Frontiers in Chemistry |
| spelling | doaj.art-34e2f4d44c6b42c0839e6eb2cf33ed882023-09-26T06:52:24ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-09-011110.3389/fchem.2023.12648241264824Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifsGbolahan O. Oduselu0Damilola V. Aderohunmu1Olayinka O. Ajani2Olayinka O. Ajani3Oluwadunni F. Elebiju4Oluwadunni F. Elebiju5Temitope A. Ogunnupebi6Temitope A. Ogunnupebi7Ezekiel Adebiyi8Ezekiel Adebiyi9Covenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, NigeriaCovenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, NigeriaCovenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, NigeriaDepartment of Chemistry, Covenant University, Ota, Ogun State, NigeriaCovenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, NigeriaDepartment of Chemistry, Covenant University, Ota, Ogun State, NigeriaCovenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, NigeriaDepartment of Chemistry, Covenant University, Ota, Ogun State, NigeriaCovenant University Bioinformatics Research (CUBRe), Covenant University, Ota, Ogun State, NigeriaDivision of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, GermanyIntroduction: Quinazolin-4(3H)-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(3H)-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(3H)-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(3H)-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 1H- and 13C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3H)-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(3H)-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.https://www.frontiersin.org/articles/10.3389/fchem.2023.1264824/fullADMETantibacterial activitiesantifungal activitiesbioactive analoghydrazoneinhibition |
| spellingShingle | Gbolahan O. Oduselu Damilola V. Aderohunmu Olayinka O. Ajani Olayinka O. Ajani Oluwadunni F. Elebiju Oluwadunni F. Elebiju Temitope A. Ogunnupebi Temitope A. Ogunnupebi Ezekiel Adebiyi Ezekiel Adebiyi Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs Frontiers in Chemistry ADMET antibacterial activities antifungal activities bioactive analog hydrazone inhibition |
| title | Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs |
| title_full | Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs |
| title_fullStr | Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs |
| title_full_unstemmed | Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs |
| title_short | Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs |
| title_sort | synthesis in silico and in vitro antimicrobial efficacy of substituted arylidene based quinazolin 4 3h one motifs |
| topic | ADMET antibacterial activities antifungal activities bioactive analog hydrazone inhibition |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1264824/full |
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