Antibacterial Activity of Quinoline‐Based Derivatives against Methicillin‐Resistant Staphylococcus aureus and Pseudomonas aeruginosa: Design, Synthesis, DFT and Molecular Dynamic Simulations
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Published:2023-11
Issue:11
Volume:20
Page:
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ISSN:1612-1872
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Container-title:Chemistry & Biodiversity
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language:en
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Short-container-title:Chemistry & Biodiversity
Author:
Sabt Ahmed1ORCID,
Abdelraof Mohamed2ORCID,
Hamissa Mohamed Farouk3,
Noamaan Mahmoud A.4
Affiliation:
1. Chemistry of Natural Compounds Department Pharmaceutical and Drug Industries Research Institute National Research Center Dokki Cairo 12622 Egypt
2. Microbial Chemistry Department Biotechnology Research Institute National Research Center (NRC) 33 El Behouth St. Giza P.O. 12622 Egypt
3. Department of Biomolecular Spectroscopy Institute of Organic Chemistry and Biochemistry Academy of Sciences Prague Czech Republic
4. Mathematics Department Faculty of Science Cairo University Giza 12613 Egypt
Abstract
AbstractBacterial virulence becomes a significant challenge for clinical treatments, particularly those characterized as Multi‐Drug‐Resistant (MDR) strains. Therefore, the preparation of new compounds with active moieties could be a successful approach for eradication of MDR strains. For this purpose, newly synthesized quinoline compounds were prepared and tested for their antimicrobial activity against Methicillin‐Resistant Staphylococcus Aureus (MRSA) and Pseudomonas Aeruginosa (PA). Among the synthesized derivatives, compounds 1‐(quinolin‐2‐ylamino)pyrrolidine‐2,5‐dione (8) and 2‐(2‐((5‐methylfuran‐2‐yl)methylene)hydrazinyl)quinoline (12) were shown to possess the highest antimicrobial activity with the minimum inhibitory concentration with the values of 5±2.2 and10±1.5 μg/mL towards Pseudomonas aeruginosa without any activity towards MRSA. Interestingly, compounds 2‐(2‐((1H‐indol‐3‐yl)methylene)hydrazinyl)quinoline (13) and 2‐(4‐bromophenyl)‐3‐(quinolin‐2‐ylamino)thiazolidin‐4‐one (16c) showed significant inhibition activity against Staphylococcus aureus MRSA and Pseudomonas aeruginosa. Compound 13 (with indole moiety) particularly displayed excellent bactericidal activity with low MIC values 20±3.3 and 10±1.5 μg/mL against Staphylococcus aureus MRSA and Pseudomonas aeruginosa, respectively. Effects molecular modelling was used to determine the mode of action for the antimicrobial effect. The stability of complexes formed by docking and target‐ligand pairing was evaluated using molecular dynamics simulations. The compounds were also tested for binding affinity to the target protein using MM‐PBSA. Density‐functional theory (DFT) calculations were also used to investigate the electrochemical properties of various compounds.
Funder
National Research Centre
Subject
Molecular Biology,Molecular Medicine,General Chemistry,Biochemistry,General Medicine,Bioengineering