| Autor: |
Singh, Vishal K., Kumari, Priyanka, Som, Anup, Rai, Shivangi, Mishra, Richa, Singh, Ramendra K. |
| Zdroj: |
Journal of Biomolecular Structure and Dynamics; September 2024, Vol. 42 Issue: 13 p6904-6924, 21p |
| Abstrakt: |
AbstractA series of new quinoline derivatives has been designed, synthesized and evaluated as antibacterial and antifungal agents functioning as peptide deformylase enzyme (PDF) inhibitors and fungal cell wall disruptors on the basis of computational and experimental methods. The molecular docking and ADMET assessment aided in the synthesis of quinoline derivatives starting from 6-amino-4-methyl-1H-quinoline-2-one substituted with different types of sulfonyl/benzoyl/propargyl moieties. These newly synthesized compounds were evaluated for their in vitroantibacterial and antifungal activity. Antibacterial screening of all compounds showed excellent MIC value (MIC, 50 − 3.12 µg/mL) against bacterial strains, viz. Bacillus cerus, Staphylococcus, Pseudomonasand Escherichia coli.Compounds 2and 6showed better activity. Fractional inhibitory concentration (FIC) values of compounds were lowered by 1/2 to 1/128 of the original MIC values when a combinatorial screening with reference drugs was performed. Further, antifungal screening against fungal strains, viz. A. flavus, A. niger, F. oxysporumand C. albicansalso showed that all compounds were potentially active and compound 6being the most potent. Further, the cytotoxicity experiments revealed that compound 6was the least toxic molecule. The molecular dynamics (MD) simulation investigations elucidated the conformational stability of compound 6-PDF complex with flexible binding pocket residues. The highest number of stable hydrogen bonds with the PDF residues during the entire simulation time illustrated strong binding affinity of compound 6with PDF.Communicated by Ramaswamy H. Sarma |
| Databáze: |
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