1. Design and synthesis of novel 1H-tetrazol-5-amine based potent antimicrobial agents: DNA topoisomerase IV and gyrase affinity evaluation supported by molecular docking studies
- Author
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Małgorzata Wrzosek, Marta Struga, Michal Kolinski, Sebastian Kmiecik, Anna Bielenica, Daniel Szulczyk, Michał A. Dobrowolski, Wioletta Olejarz, Michał Jóźwiak, Piotr Roszkowski, and Joanna Stefańska
- Subjects
DNA Topoisomerase IV ,Models, Molecular ,0301 basic medicine ,Topoisomerase IV ,Stereochemistry ,Tetrazoles ,Microbial Sensitivity Tests ,01 natural sciences ,DNA gyrase ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Discovery ,Humans ,Topoisomerase II Inhibitors ,Tetrazole ,Triethylamine ,Amination ,Pharmacology ,Bacteria ,biology ,010405 organic chemistry ,Organic Chemistry ,Bacterial Infections ,General Medicine ,Antimicrobial ,Anti-Bacterial Agents ,0104 chemical sciences ,Molecular Docking Simulation ,030104 developmental biology ,Thiourea ,chemistry ,DNA Gyrase ,Drug Design ,biology.protein ,Sodium azide ,Amine gas treating - Abstract
A total of 14 of 1,5-disubstituted tetrazole derivatives were prepared by reacting appropriate thiourea and sodium azide in the presence of mercury (II) chloride and triethylamine. All compounds were evaluated in vitro for their antimicrobial activity. Derivatives 10 and 11 showed the highest inhibition against Gram-positive and Gram-negative strains (standard and hospital strains). The observed minimal inhibitory concentrations values were in the range of 1–208 μM (0.25–64 μg/ml). Inhibitory activity of 1,5-tetrazole derivatives 10 and 11 against gyrase and topoisomerase IV isolated from S. aureus was studied. Evaluation was supported by molecular docking studies for all synthesized derivatives and reference ciprofloxacin. Moreover, selected tetrazoles (2, 3, 5, 6, 8, 9, 10 and 11) were evaluated for their cytotoxicity. All tested compounds are non-cytotoxic against HaCaT and A549 cells (CC50 ≤ 60 μM).
- Published
- 2018