Co(II) and Cu(II) pyrophosphate complexes have selectivity and potency against Mycobacteria including Mycobacterium tuberculosis

Abstract

Tuberculosis (TB) causes up to 10 million incident cases worldwide per annum. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains are leading factors in the resurgence of TB cases and the need to produce new agents to combat such infection. Herein, we describe Co(II) and Cu(II) metal based complexes that feature the pyrophosphate ligand with notable selectivity and marked potency against Mycobacterium tuberculosis, including MDR strains. Such complexes are confirmed to be bacteriocidal and not affected by efflux inhibitors. Finally, while susceptibility to copper has recently been established for M. tuberculosis, the greater efficacy of cobalt observed herein is of considerable note and in line with the discovery of a copper metallothionein in M. tuberculosis.

Keywords: Bacteriocidal; Cobalt; Copper; INH; MDR-TB; MIC; MOTT; Mycobacteria other than TB; Pyrophosphate; TB; XDR-TB; extensively drug-resistant TB; isoniazid; minimum inhibitory concentration; multidrug-resistant TB; tuberculosis.