Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents

Frontiers in Microbiology

Microbiology

Baye Sitotaw¹  Farid Khallouki²  Mohammed Bourhia³  Yousef A. Bin Jardan⁴  Lahcen Ouahmane⁵  Guojun Zheng⁶  Muhammad Shahab⁶ 

[1] Department of Biology, Bahir Dar University, Bahir Dar, Ethiopia;Department of Biology, FSTE, University Moulay Ismail, Errachidia, Morocco;Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, Morocco;Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;Laboratory of Microbial Biotechnologies, Agrosciences and Environment (BioMAgE), Labeled Research Unit-CNRSTN°4, Cadi Ayyad University, Marrakesh, Morocco;State Key Laboratories of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing, China;

关键词: Staphylococcus aureus;    napthyridine;    molecular docking;    molecular dynamics simulation;    quantum mechanical calculation;   

DOI  :  10.3389/fmicb.2023.1279082

 received in 2023-08-17, accepted in 2023-09-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

The disease-free existence of humans is constantly under attack by a variety of infections caused by a variety of organisms including bacteria. Notable among the bacteria is Staphylococcus aureus which is an etiological organism for infections including impetigo, folliculitis, and furuncles. The response of the human immune system against this disease is often neutralized by the production of a pigment called Staphyloxanthin (STX) via a series of reactions mediated by several enzymes. Among these enzymes, dehydrosqualene synthase, also known as CrtM, has emerged as a viable drug target due to its role in mediating the first step of the pathway. Consequently, this study employs molecular modeling approaches including molecular docking, quantum mechanical calculations, and molecular dynamics (MD) simulations among others to investigate the potential of napthyridine derivatives to serve as inhibitors of the CrtM. The results of the study revealed the high binding affinities of the compounds for the target as demonstrated by their docking scores, while further subjection to screening pipeline aimed at determining their fitness for development into drugs revealed just one compound namely 6-[[1-[(2-fluorophenyl) methyl]triazol-4-yl]methoxy]-4-oxo-1H-1,5-naphthyridine-3-carboxylic acid as the compound with good drug-like, pharmacokinetics, and toxicity properties profiles. A 100 ns-long MD simulation of the complexes formed after molecular docking revealed the stable interaction of the compound with the target. Ultimately, this study can be a promising outlet to discover a weapon to fight against clinically resistant bacteria, however, further experimental studies are suggested to carry out in the wet lab, pre-clinical, and clinical levels.

【 授权许可】

Unknown   
Copyright © 2023 Bourhia, Shahab, Zheng, Bin Jardan, Sitotaw, Ouahmane and Khallouki.