Development and radiosterilization of new hydrazono-quinoline hybrids as DNA gyrase and topoisomerase IV inhibitors: Antimicrobial and hemolytic activities against uropathogenic isolates with molecular docking study.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101262549 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1747-0285 (Electronic) Linking ISSN: 17470277 NLM ISO Abbreviation: Chem Biol Drug Des Subsets: MEDLINE

Original Publication: Oxford : Wiley-Blackwell, 2006-

DNA Gyrase*/metabolism ; Anti-Infective Agents*/pharmacology; Molecular Docking Simulation ; DNA Topoisomerase IV/metabolism ; Topoisomerase II Inhibitors/pharmacology ; Topoisomerase II Inhibitors/chemistry ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/chemistry ; Microbial Sensitivity Tests ; Structure-Activity Relationship ; Molecular Structure

This study aimed to synthesize new potent quinoline derivatives based on hydrazone moieties and evaluate their antimicrobial activity. The newly synthesized hydrazono-quinoline derivatives 2, 5a, 9, and 10b showed the highest antimicrobial activity with MIC values ≤1.0 μg/ml against bacteria and ≤8.0 μg/ml against the fungi. Further, these derivatives exhibited bactericidal and fungicidal effects with MBC/MIC and MFC/MIC ratio ≤4. Surprisingly, the most active compounds displayed good inhibition to biofilm formation with MBEC values ranging between (40.0 ± 10.0 - 230.0 ± 31.0) and (67.0 ± 24.0 - 347.0 ± 15.0) μg/ml against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. The hemolytic assays confirmed that the hydrazono-quinoline derivatives are non-toxic with low % lysis values ranging from 4.62% to 14.4% at a 1.0 mg/ml concentration. Besides, compound 5a exhibited the lowest hemolytic activity value of ~4.62%. Furthermore, the study suggests that the hydrazono-quinoline analogs exert their antibacterial activity as dual inhibitors for DNA gyrase and DNA topoisomerase IV enzymes with IC 50 values ranging between (4.56 ± 0.3 - 21.67 ± 0.45) and (6.77 ± 0.4 - 20.41 ± 0.32) μM, respectively. Additionally, the recent work advocated that compound 5a showed the reference SAL at the ɣ-radiation dose of 10.0 kGy in the sterilization process without affecting its chemical structure. Finally, the in silico drug-likeness, toxicity properties, and molecular docking simulation were performed. Besides, the result exhibited good oral-bioavailability, lower toxicity prediction, and lower binding energy with good binding mode rather than the positive control.
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Keywords: ADMET; DNA gyrase and DNA topoisomerase IV; UTIs; hemolytic activity; molecular docking; quinolines; ɣ-radiation

EC 5.99.1.3 (DNA Gyrase)
EC 5.99.1.- (DNA Topoisomerase IV)
0 (Topoisomerase II Inhibitors)
0 (Anti-Infective Agents)
0 (Anti-Bacterial Agents)

Date Created: 20221028 Date Completed: 20230113 Latest Revision: 20230214

20230215

10.1111/cbdd.14154

36305722