{"title":"Structural toxicity relationship (STR) of linezolid to mitigate myelosuppression and serotonergic toxicity","authors":"Matin Shaikh , Harun Patel","doi":"10.1016/j.bmc.2024.118025","DOIUrl":null,"url":null,"abstract":"<div><div>Tuberculosis (TB) remains a significant global health challenge, with multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains posing severe threats to treatment efficacy. Linezolid, a key component of the BPaL (Bedaquiline, Pretomanid and Linezolid) regimen, has demonstrated substantial efficacy against MDR-TB and XDR-TB. However, its clinical utility is often limited by side effects such as myelosuppression and monoamine oxidase (MAO) inhibition, linked to its mechanism of action. This perspective centres on the structural toxicity relationship (STR) of Linezolid and its analogues, exploring modifications to the C-ring and C-5 position that aim to reduce these toxicities while maintaining or enhancing antibacterial activity. Several promising analogues have been identified that exhibit reduced myelosuppression and MAO inhibition, highlighting the potential for developing safer Linezolid derivatives. The findings underscore the importance of continued research into the structure toxicity relationships of oxazolidinones to improve the therapeutic profiles of these essential drugs in combating drug-resistant TB.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"118 ","pages":"Article 118025"},"PeriodicalIF":3.3000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0968089624004395","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Tuberculosis (TB) remains a significant global health challenge, with multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains posing severe threats to treatment efficacy. Linezolid, a key component of the BPaL (Bedaquiline, Pretomanid and Linezolid) regimen, has demonstrated substantial efficacy against MDR-TB and XDR-TB. However, its clinical utility is often limited by side effects such as myelosuppression and monoamine oxidase (MAO) inhibition, linked to its mechanism of action. This perspective centres on the structural toxicity relationship (STR) of Linezolid and its analogues, exploring modifications to the C-ring and C-5 position that aim to reduce these toxicities while maintaining or enhancing antibacterial activity. Several promising analogues have been identified that exhibit reduced myelosuppression and MAO inhibition, highlighting the potential for developing safer Linezolid derivatives. The findings underscore the importance of continued research into the structure toxicity relationships of oxazolidinones to improve the therapeutic profiles of these essential drugs in combating drug-resistant TB.
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.