2. Academic Validation
  3. Antituberculosis Activity of the Antimalaria Cytochrome bcc Oxidase Inhibitor SCR0911

Antituberculosis Activity of the Antimalaria Cytochrome bcc Oxidase Inhibitor SCR0911

  • ACS Infect Dis. 2020 Apr 10;6(4):725-737. doi: 10.1021/acsinfecdis.9b00408.
Shi Min Sherilyn Chong 1 2 3,  Malathy Sony Subramanian Manimekalai 1,  Jickky Palmae Sarathy 4,  Zoe C Williams 5,  Liam K Harold 5,  Gregory M Cook 5,  Thomas Dick 4 6,  Kevin Pethe 1 7,  Roderick W Bates 2,  Gerhard Grüber 1
Affiliations

Affiliations

  • 1 School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Republic of Singapore.
  • 2 School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Republic of Singapore.
  • 3 Nanyang Institute of Technology in Health and Medicine, Interdisciplinary Graduate School, Nanyang Technological University, Singapore 637551, Republic of Singapore.
  • 4 Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore 117599, Republic of Singapore.
  • 5 Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
  • 6 Center for Discovery and Innovation, Hackensack Meridian Health, 340 Kingsland Street Building 102, Nutley, New Jersey 07110, United States.
  • 7 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore.
PMID: 32092260 DOI: 10.1021/acsinfecdis.9b00408
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.

Keywords

Mycobacteria; OXPHOS pathway; Q203; Telacebec; Tuberculosis; extremely drug resistance; multidrug resistance.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-182711
    分枝杆菌细胞色素bcc氧化酶抑制剂/恶性疟原虫细胞色素bc1结合剂
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