Computational Screening of Novel Nitroimidazole Candidates: Targeting Key Enzymes of Oral Anaerobes for Anti-Parasitic Potential.

Autor:	Lanez T; VTRS Laboratory, Department of Chemistry, Faculty of Sciences, University of El Oued B.P.789, 39000, El Oued, Algeria., Lanez M; Department of Biochemistry, Faculty of Natural and Life Sciences, University of El Oued B.P.789, 39000, El Oued, Algeria., Lanez R; Department of Biochemistry, Faculty of Natural and Life Sciences, University of El Oued B.P.789, 39000, El Oued, Algeria., Lanez E; Department of Biochemistry, Faculty of Natural and Life Sciences, University of El Oued B.P.789, 39000, El Oued, Algeria., Talbi-Lanez B; Department of Biochemistry, Faculty of Natural and Life Sciences, University of El Oued B.P.789, 39000, El Oued, Algeria.
Jazyk:	angličtina
Zdroj:	Current drug discovery technologies [Curr Drug Discov Technol] 2024 Nov 05. Date of Electronic Publication: 2024 Nov 05.
DOI:	10.2174/0115701638326365241029080310
Abstrakt:	Background: The study focuses on evaluating the parasitic potential of novel metronidazole analogs using computational methods. Specifically, it aims to target key enzymes of oral anaerobes, including UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA) of Fusobacterium nucleatum and DNA topoisomerase (Topo) of Prevotella intermedia. Objective: The objective is to assess the pharmacokinetic and toxicity properties of 368 novel nitroimidazole candidates through virtual screening. Additionally, the study aims to determine the binding affinity of the most promising candidates with the target proteins through molecular docking analyses. Methods: A combinatorial library of nitroimidazole candidates was constructed, and virtual screening was performed. Molecular docking analyses were conducted to evaluate the binding affinity of selected compounds with MurA and Topo. Further investigation involved molecular dynamic simulation to assess the stability of the compounds within the active sites of MurA and Topo. Results: All selected compounds exhibited activity against both MurA and Topo. Among them, Mnz11, Mnz12, and Mnz15 demonstrated the lowest binding free energies and IC50 values. Molecular dynamic simulation indicated that these three compounds remained stable within the active sites of MurA and Topo, with RMSD values consistently below 2Å. Additionally, the antibacterial potential of the most potent compound, Mnz15, was evaluated against a series of oral microbes. Conclusion: The study concludes that the newly identified nitroimidazole candidates show promise as anti-parasitic agents, based on their activity against key enzymes of oral anaerobes and their pharmacokinetic properties evaluated through computational methods. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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