Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911
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 mycoba...
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sg-ntu-dr.10356-1388322023-02-28T17:09:44Z Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911 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 School of Biological Sciences School of Physical and Mathematical Sciences Interdisciplinary Graduate School (IGS) Lee Kong Chian School of Medicine (LKCMedicine) Nanyang Institute of Technology in Health and Medicine Science::Biological sciences::Biochemistry Science::Biological sciences::Microbiology Tuberculosis Mycobacteria 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. NRF (Natl Research Foundation, S’pore) Accepted version 2020-05-13T04:50:31Z 2020-05-13T04:50:31Z 2020 Journal Article 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 2373-8227 https://hdl.handle.net/10356/138832 10.1021/acsinfecdis.9b00408 32092260 4 6 725 737 en ACS Infectious Diseases 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 https://doi.org/10.1021/acsinfecdis.9b00408 application/pdf |
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Science::Biological sciences::Biochemistry Science::Biological sciences::Microbiology Tuberculosis Mycobacteria 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 Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911 |
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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. |
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School of Biological Sciences |
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School of Biological Sciences 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 |
format |
Article |
author |
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 |
author_sort |
Chong, Sherilyn Shi Min |
title |
Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911 |
title_short |
Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911 |
title_full |
Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911 |
title_fullStr |
Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911 |
title_full_unstemmed |
Antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor SCR0911 |
title_sort |
antituberculosis activity of the antimalaria cytochrome bcc oxidase inhibitor scr0911 |
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2020 |
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https://hdl.handle.net/10356/138832 |
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1759854579190595584 |