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

Abstract

The observations that the innate immune system employs copper toeliminate bacterial infection and that resistance to copper enhancesvirulence ofMycobacterium tuberculosis(Mtb) prompted us to exam-ine the effects the anti-cancer agent elesclomol onMtb.As a bis-thio-nohydrazide, elesclomol chelates with copper to form a coppercomplex in situ that via redox cycling of the metal ion greatlyenhances oxidative stress in tumour cells. Here, we demonstrate thatelesclomol is relatively potent againstMtbH37Rv with minimum inhib-itory concentration of 10μM (4 mg/L) and against multidrug resistantclinical isolates ofMtb, displays additive interactions with knowntuberculosis drugs such as isoniazid and ethambutol, and a synergisticinteraction with rifampicin. Controlled supplementation of elesclomolwith copper in culture medium increasedMtbsensitivity by >65 fold.Overall, the activities of elesclomol in principle indicate the possibilityof repurposing elesclomol or designing new thionohydrazides aspotential drugs for use againstMtb