Antituberculosis Activity of the Antimalaria Cytochrome Oxidase Inhibitor SCR0911.

The ability to respire and generate adenosine triphosphate (ATP) is essential for the physiology, persistence, and pathogenicity of , which causes tuberculosis. By employing a lead repurposing strategy, the malarial cytochrome 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 . Whole-cell-based and assays demonstrated the potency of SCR0911 by inhibiting cell growth and ATP synthesis in both the fast- and slow-growing and bacillus Calmette-Guérin, respectively. The variety of biochemical assays and the use of a cytochrome deficient mutant strain validated the cytochrome 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.