Halogenated N-(1,3,4-oxadiazol-2-yl) benzamides are effective eradicators of methicillin-resistant Staphylococcus aureus biofilms

IF 3.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2026-01-01 Epub Date: 2025-10-09 DOI:10.1016/j.bmc.2025.118437

George A. Naclerio , Christopher S. Vennard , Kenneth I. Onyedibe , Dielson da S. Vieira , Nader S. Abutaleb , Marxa L. Figueiredo , Mohamed N. Seleem , Herman O. Sintim

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Abstract

Due to the ever-increasing threat of methicillin-resistant Staphylococcus aureus (MRSA), we have embarked on a campaign to discover novel antibacterial agents which are effective at eradicating both MRSA, as well as acting on pre-formed MRSA biofilms. Using the known scaffold of N-(1,3,4-oxadiazol-2-yl)benzamides, we performed a halogenation study which has led to the identification of HSGN-2241. This novel compound was found to effectively kill many multi-drug resistant Gram-positive clinical isolates in a bactericidal manner. The growth inhibition mechanism of HSGN-2241 was found to be via potassium ion release and subsequent depolarization of the cell membrane. As an initial safety test, HSGN-2241 was found to not lyse human red blood cells, so it is a promising lead compound for the treatment of bacterial infections caused by Staphylococcus aureus.

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卤化N-（1,3,4-恶二唑-2-基）苯酰胺是耐甲氧西林金黄色葡萄球菌生物膜的有效根除剂。

由于耐甲氧西林金黄色葡萄球菌（MRSA）的威胁日益增加，我们已经开始了一项运动，以发现新的抗菌剂，既能有效地根除MRSA，又能作用于预形成的MRSA生物膜。利用已知的N-（1,3,4-恶二唑-2-基）苯酰胺支架，我们进行了卤化研究，最终鉴定出HSGN-2241。这种新型化合物被发现能以杀菌方式有效地杀死许多多重耐药革兰氏阳性临床分离株。发现HSGN-2241的生长抑制机制是通过钾离子释放和随后的细胞膜去极化。作为初步的安全性试验，HSGN-2241被发现不会溶解人体红细胞，因此它是治疗金黄色葡萄球菌引起的细菌感染的有希望的先导化合物。

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.