Pallavi Saha, Shashikanta Sau, Nitin Pal Kalia and Deepak K. Sharma
{"title":"Antitubercular activity of 2-mercaptobenzothiazole derivatives targeting Mycobacterium tuberculosis type II NADH dehydrogenase†","authors":"Pallavi Saha, Shashikanta Sau, Nitin Pal Kalia and Deepak K. Sharma","doi":"10.1039/D4MD00118D","DOIUrl":null,"url":null,"abstract":"<p >\r\n <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) type II NADH dehydrogenase (NDH-2) transports electrons into the mycobacterial respiratory pathway at the cost of reduction of NADH to NAD<small><sup>+</sup></small> and is an attractive drug target. Herein, we have synthesised a series of 2-mercaptobenzothiazoles (<strong>C1–C14</strong>) and evaluated their anti-tubercular potential as <em>Mtb</em> NDH-2 inhibitors. The synthesised compounds <strong>C1–C14</strong> were evaluated for MIC<small><sub>90</sub></small> and ATP depletion against <em>Mtb</em> H37Ra, <em>M. bovis</em>, and <em>Mtb</em> H37Rv mc<small><sup>2</sup></small> 6230. Compounds <strong>C3</strong>, <strong>C4</strong>, and <strong>C11</strong> were found to be the active molecules in the series and were further evaluated for their MIC<small><sub>90</sub></small> against <em>Mtb</em>-resistant strains and for their bactericidal potential against <em>Mtb</em> H37Rv mc<small><sup>2</sup></small>6230. The Peredox-mCherry-expressing <em>Mtb</em> strain was used to examine whether <strong>C3</strong>, <strong>C4</strong>, and <strong>C11</strong> possess NDH-2 inhibitory potential. Furthermore, cytotoxicity analysis against HepG2 displayed a safety index (SI) of >10 for <strong>C3</strong> and <strong>C4</strong>. To get an insight into the mode of interaction at NDH-2, we have performed computational analysis of our active compounds.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"RSC medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/md/d4md00118d","RegionNum":4,"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
Mycobacterium tuberculosis (Mtb) type II NADH dehydrogenase (NDH-2) transports electrons into the mycobacterial respiratory pathway at the cost of reduction of NADH to NAD+ and is an attractive drug target. Herein, we have synthesised a series of 2-mercaptobenzothiazoles (C1–C14) and evaluated their anti-tubercular potential as Mtb NDH-2 inhibitors. The synthesised compounds C1–C14 were evaluated for MIC90 and ATP depletion against Mtb H37Ra, M. bovis, and Mtb H37Rv mc2 6230. Compounds C3, C4, and C11 were found to be the active molecules in the series and were further evaluated for their MIC90 against Mtb-resistant strains and for their bactericidal potential against Mtb H37Rv mc26230. The Peredox-mCherry-expressing Mtb strain was used to examine whether C3, C4, and C11 possess NDH-2 inhibitory potential. Furthermore, cytotoxicity analysis against HepG2 displayed a safety index (SI) of >10 for C3 and C4. To get an insight into the mode of interaction at NDH-2, we have performed computational analysis of our active compounds.