Synthesis and antitubercular activity of novel 4-arylalkyl substituted thio-, oxy- and sulfoxy-quinoline analogues targeting the cytochrome bc1 complex

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dc.cclicenceCC BYen
dc.contributor.authorMurnane, Robert
dc.contributor.authorBrucoli, Federico
dc.contributor.authorTanna, Sangeeta
dc.contributor.authorAllen, Renee
dc.contributor.authorSantana-Gomez, Felipe
dc.contributor.authorParish, Tanya
dc.contributor.authorZloh, Mire
dc.date.acceptance2023-06-05
dc.date.accessioned2023-07-13T15:54:37Z
dc.date.available2023-07-13T15:54:37Z
dc.date.issued2023-06-05
dc.descriptionopen access articleen
dc.description.abstractA library of 4-substituted quinolines was synthesised based on the structural features of the privileged 4-(benzylthio)-6-methoxy-2-methylquinoline scaffold. Quinoline-based chemical probes have proven to be effective anti-tuberculosis agents with the ability of inhibiting components of Mycobacterium tuberculosis (MTB) respiratory chain including the b subunit of the cytochrome bc1 complex. Novel 4-(arylalkyl)-thio, -oxy and sulfoxy-quinoline analogues were tested for their ability to inhibit the growth of MTB H37Rv and QcrB mutant strains, and the compounds mode of action was investigated. Members of the 4-subtituted thio- and sulfoxyquinoline series exhibited significant growth inhibitory activity in the high nanomolar range against wild-type MTB and induced depletion of intracellular ATP. These probes also showed reduced potency in the QcrB T313I mutant strain, thus indicating the cytochrome bc1 oxidase complex as the molecular target. Interestingly, new 4-(quinolin-2-yl)oxy-quinoline 4i was more selective for the QcrB T313I strain compared to the wild-type strain.en
dc.funderNo external funderen
dc.identifier.citationMurnane, R., Zloh, M., Tanna, S., Allen, R., Santana-Gomez, F., Parish, T. and Brucoli, F. (2023) Synthesis and antitubercular activity of novel 4-arylalkyl substituted thio-, oxy- and sulfoxy-quinoline analogues targeting the cytochrome bc1 complex. Bioorganic Chemistry, 138, 106659en
dc.identifier.doihttps://doi.org/10.1016/j.bioorg.2023.106659
dc.identifier.issn0045-2068
dc.identifier.urihttps://hdl.handle.net/2086/23103
dc.language.isoenen
dc.peerreviewedYesen
dc.publisherElsevieren
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en
dc.titleSynthesis and antitubercular activity of novel 4-arylalkyl substituted thio-, oxy- and sulfoxy-quinoline analogues targeting the cytochrome bc1 complexen
dc.typeArticleen

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