Journal
JOURNAL OF MOLECULAR STRUCTURE
Volume 1242, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.molstruc.2021.130748
Keywords
7-ethoxy quinoline; Antimicrobial activity; MBC; MDRB; DHFR; Molecular docking; molecular electrostatic potential by DFT
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The study involved synthesis of quinoline-based thiazole analogues for antibiotic class, which showed good antimicrobial activity against standard microbial pathogens and MDR bacterial strains. Active derivatives were effective in treating bacterial infection by inhibiting DHFR enzyme, with molecular docking study supporting the binding mode. DFT calculation generated MEP surfaces to determine interaction regions for different types of interactions.
Over the world and especially the developing countries, one of the major threats to human health is antibiotic resistance due to antibiotics abuse. This challenge can be solved by discovering new targets and inhibitors. The current study involved synthesis quinoline based thiazole analogues for quinoline an-tibiotic class using classic organic synthesis. The designed derivatives were tested against eight standard microbial pathogens. Among them, seven derivatives showed good antimicrobial activity with MIC and MBC values ranged between (0.97-62.5) mu g/mL, and (1.94-118.7) mu g/mL, respectively. Additionally, the active derivatives displayed good activity against three MDR bacterial stains. Compounds 11b , and 5a ex-hibited to be the most active derivatives against S. aureus and E. coli with MIC (1.95-7.81) mu g/mL and MBC (3.31-15.62) mu g/mL followed by other derivatives compared with Ciprofloxacin and Vancomycin. Be-sides, compounds 6, 11c , and 15 appeared the most active derivatives against MDR P. aeruginosa with MIC and MBC values lower than 10 mu g/mL. These derivatives considered effective for treating bacterial infec-tion by inhibiting DHFR enzyme that showed IC50 values (10.02-25.11) mu M in comparison to Trimetho-prim (18.95 mu M). Molecular docking study against DHFR enzyme (1DLS) was carried out, and the active derivatives bind to some the nearly the same amino acid residues as MTX that support our hypothesis. Furthermore, the MEP surfaces were generated using DFT calculation to determine the regions might be responsible for forming different types of interaction and confirm the binding mode in docking study. (C) 2021 Elsevier B.V. All rights reserved.
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