title: 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.
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, NY 13244, United States.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Hoffman
authors.forename: Michelle
authors.initials: M
authors.lastname: DeStefano
authors.forename: Carolyn
authors.initials: C
authors.lastname: Shoen
authors.forename: Krishnamoorthy
authors.initials: K
authors.lastname: Gopinath
authors.forename: Digby F
authors.initials: DF
authors.lastname: Warner
authors.forename: Michael
authors.initials: M
authors.lastname: Cynamon
authors.forename: Robert P
authors.initials: RP
authors.lastname: Doyle
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003035:Cobalt / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D011756:Diphosphates / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009161:Mycobacterium / Q000187:drug effects*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011756:Diphosphates; D009942:Organometallic Compounds; D003035:Cobalt; C107241:diphosphoric acid; D003300:Copper
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