The evaluation of the anti ‐cancer drug elesclomol that forms a redox‐active copper chelate as a potential anti‐tubercular drug

AbstractThe observations that the innate immune system employs copper to eliminate bacterial infection and that resistance to copper enhances virulence ofMycobacterium tuberculosis (Mtb) prompted us to examine the effects the anti ‐cancer agent elesclomol onMtb. As a bis ‐thionohydrazide, elesclomol chelates with copper to form a copper complex in situ that via redox cycling of the metal ion greatly enhances oxidative stress in tumour cells. Here, we demonstrate that elesclomol is relatively potent againstMtb H37Rv with minimum inhibitory concentration of 10 μM (4 mg/L) and against multidrug resistant clinical isolates ofMtb, displays additive interactions with known tuberculosis drugs such as isoniazid and ethambutol, and a synergistic interaction with rifampicin. Controlled supplementation of elesclomol with copper in culture medium increasedMtb sensitivity by>65 fold. Overall, the activities of elesclomol in principle indicate the possibility of repurposing elesclomol or designing new thionohydrazides as potential drugs for use againstMtb. © 2019 IUBMB Life, 2019
Source: IUBMB Life - Category: Research Authors: Tags: Hypothesis Source Type: research