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

European Journal Of Medicinal Chemistry, 156, 631-640, 2018

Authors: Szulczyk Daniel, Dobrowolski Michal A., Roszkowski Piotr, Bielenica Anna, Stefanska Joanna, Kolinski Michal, Kmiecik Sebastian, Jozwiak Michal, Wrzosek Malgorzata, Olejarz Wioletta, Struga Marta


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 mu M (0.25-64 mu g/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 mu M). (C) 2018 Elsevier Masson SAS. All rights reserved.