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Novel Tetrazole-Based Antimicrobial Agents Targeting Clinical Bacteria Strains: Exploring the Inhibition of Staphylococcus aureus DNA Topoisomerase IV and Gyrase

Authors :
Piotr Roszkowski
Jolanta Szymańska-Majchrzak
Michał Koliński
Sebastian Kmiecik
Małgorzata Wrzosek
Marta Struga
Daniel Szulczyk
Source :
International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 378, International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 23, Iss 378, p 378 (2022)
Publication Year :
2021
Publisher :
Multidisciplinary Digital Publishing Institute, 2021.

Abstract

Eleven novel imide-tetrazoles were synthesized. In the initial stage of research, in silico structure-based pharmacological prediction was conducted. All compounds were screened for antimicrobial activity using standard and clinical strains. Within the studied group, compounds 1–3 were recognized as leading structures with the most promising results in antimicrobial studies. Minimal inhibitory concentration values for compounds 1, 2, 3 were within the range of 0.8–3.2 μg/mL for standard and clinical Gram-positive and Gram-negative bacterial strains, showing in some cases higher activity than the reference Ciprofloxacin. Additionally, all three inhibited the growth of all clinical Staphylococci panels: Staphylococcus aureus (T5592; T5591) and Staphylococcus epidermidis (5253; 4243) with MIC values of 0.8 μg/mL. Selected compounds were examined in topoisomerase IV decatenation assay and DNA gyrase supercoiling assay, followed by suitable molecular docking studies to explore the possible binding modes. In summary, the presented transition from substrate imide-thioureas to imide-tetrazole derivatives resulted in significant increase of antimicrobial properties. The compounds 1–3 proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates.

Details

Language :
English
ISSN :
14220067
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 378
Accession number :
edsair.doi.dedup.....c4d253f9ba3673d152e21b90c8bae571
Full Text :
https://doi.org/10.3390/ijms23010378