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Title: Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911
Authors: Chong, Sherilyn Shi Min
Manimekalai, Malathy Sony Subramanian
Sarathy, Jickky Palmae
Williams, Zoe C.
Harold, Liam K.
Cook, Gregory M.
Dick, Thomas
Pethe, Kevin
Bates, Roderick Wayland
Grüber, Gerhard
Keywords: Science::Biological sciences::Biochemistry
Science::Biological sciences::Microbiology
Issue Date: 2020
Source: Chong, S. S. M., Manimekalai, M. S. S., Sarathy, J. P., Williams, Z. C., Harold, L. K., Cook, G. M., . . . Grüber, G. (2020). Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911. ACS Infectious Diseases, 6(4), 725-737. doi:10.1021/acsinfecdis.9b00408
Journal: ACS Infectious Diseases
Abstract: The ability to respire and generate adenosine triphosphate (ATP) is essential for the physiology, persistence, and pathogenicity of Mycobacterium tuberculosis, which causes tuberculosis. By employing a lead repurposing strategy, the malarial cytochrome bc1 inhibitor SCR0911 was tested against mycobacteria. Docking studies were carried out to reveal potential binding and to understand the binding interactions with the target, cytochrome bcc. Whole-cell-based and in vitro assays demonstrated the potency of SCR0911 by inhibiting cell growth and ATP synthesis in both the fast- and slow-growing M. smegmatis and M. bovis bacillus Calmette–Guérin, respectively. The variety of biochemical assays and the use of a cytochrome bcc deficient mutant strain validated the cytochrome bcc oxidase as the direct target of the drug. The data demonstrate the broad-spectrum activity of SCR0911 and open the door for structure–activity relationship studies to improve the potency of new mycobacteria specific SCR0911 analogues.
ISSN: 2373-8227
DOI: 10.1021/acsinfecdis.9b00408
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Infectious Diseases, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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