Luke R. Churchman , James R. Beckett , Lendl Tan , Kyra Woods , Daniel Z. Doherty , Amna Ghith , Paul V. Bernhardt , Stephen G. Bell , Nicholas P. West , James J. De Voss
{"title":"Synthesis of steroidal inhibitors for Mycobacterium tuberculosis","authors":"Luke R. Churchman , James R. Beckett , Lendl Tan , Kyra Woods , Daniel Z. Doherty , Amna Ghith , Paul V. Bernhardt , Stephen G. Bell , Nicholas P. West , James J. De Voss","doi":"10.1016/j.jsbmb.2024.106479","DOIUrl":null,"url":null,"abstract":"<div><p>Oxidised derivatives of cholesterol have been shown to inhibit the growth of <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>). The bacteriostatic activity of these compounds has been attributed to their inhibition of CYP125A1 and CYP142A1, two metabolically critical cytochromes P450 that initiate degradation of the sterol side chain. Here, we synthesise and characterise an extensive library of 28 cholesterol derivatives to develop a structure-activity relationship for this class of inhibitors. The candidate compounds were evaluated for MIC with virulent <em>Mtb</em> and in binding studies with CYP125A1 and CYP142A1 from <em>Mtb.</em></p></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"239 ","pages":"Article 106479"},"PeriodicalIF":2.5000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Steroid Biochemistry and Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S096007602400027X","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/10 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Oxidised derivatives of cholesterol have been shown to inhibit the growth of Mycobacterium tuberculosis (Mtb). The bacteriostatic activity of these compounds has been attributed to their inhibition of CYP125A1 and CYP142A1, two metabolically critical cytochromes P450 that initiate degradation of the sterol side chain. Here, we synthesise and characterise an extensive library of 28 cholesterol derivatives to develop a structure-activity relationship for this class of inhibitors. The candidate compounds were evaluated for MIC with virulent Mtb and in binding studies with CYP125A1 and CYP142A1 from Mtb.
期刊介绍：
The Journal of Steroid Biochemistry and Molecular Biology is devoted to new experimental and theoretical developments in areas related to steroids including vitamin D, lipids and their metabolomics. The Journal publishes a variety of contributions, including original articles, general and focused reviews, and rapid communications (brief articles of particular interest and clear novelty). Selected cutting-edge topics will be addressed in Special Issues managed by Guest Editors. Special Issues will contain both commissioned reviews and original research papers to provide comprehensive coverage of specific topics, and all submissions will undergo rigorous peer-review prior to publication.
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