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Article

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

1
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warszawa, Poland
2
Chair and Department of Biochemistry, Medical University of Warsaw, 02-097 Warszawa, Poland
3
Bioinformatics Laboratory, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego St., 02-106 Warsaw, Poland
4
Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, 02-089 Warsaw, Poland
5
Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Michał Arabski
Int. J. Mol. Sci. 2022, 23(1), 378; https://doi.org/10.3390/ijms23010378
Received: 3 December 2021 / Revised: 22 December 2021 / Accepted: 28 December 2021 / Published: 29 December 2021
(This article belongs to the Special Issue New Antibacterial Agents)
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 13 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 13 proposed here provide a promising basis for further exploration towards novel antimicrobial drug candidates. View Full-Text
Keywords: antimicrobial; antibacterial; tetrazole; gyrase; topoisomerase antimicrobial; antibacterial; tetrazole; gyrase; topoisomerase
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MDPI and ACS Style

Roszkowski, P.; Szymańska-Majchrzak, J.; Koliński, M.; Kmiecik, S.; Wrzosek, M.; Struga, M.; Szulczyk, D. Novel Tetrazole-Based Antimicrobial Agents Targeting Clinical Bacteria Strains: Exploring the Inhibition of Staphylococcus aureus DNA Topoisomerase IV and Gyrase. Int. J. Mol. Sci. 2022, 23, 378. https://doi.org/10.3390/ijms23010378

AMA Style

Roszkowski P, Szymańska-Majchrzak J, Koliński M, Kmiecik S, Wrzosek M, Struga M, Szulczyk D. Novel Tetrazole-Based Antimicrobial Agents Targeting Clinical Bacteria Strains: Exploring the Inhibition of Staphylococcus aureus DNA Topoisomerase IV and Gyrase. International Journal of Molecular Sciences. 2022; 23(1):378. https://doi.org/10.3390/ijms23010378

Chicago/Turabian Style

Roszkowski, Piotr, Jolanta Szymańska-Majchrzak, Michał Koliński, Sebastian Kmiecik, Małgorzata Wrzosek, Marta Struga, and Daniel Szulczyk. 2022. "Novel Tetrazole-Based Antimicrobial Agents Targeting Clinical Bacteria Strains: Exploring the Inhibition of Staphylococcus aureus DNA Topoisomerase IV and Gyrase" International Journal of Molecular Sciences 23, no. 1: 378. https://doi.org/10.3390/ijms23010378

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