Enhanced Bactericidal Effects of Pyrazinamide Toward Mycobacterium smegmatis and Mycobacterium tuberculosis upon Conjugation to a {Au(I)-triphenylphosphine}+ Moiety

Abstract As part of the quest for new gold drugs, we have explored the efficacy of three gold complexes derived from the tuberculosis drug pyrazinamide (PZA), namely, the gold(I) complex [Au(PPh3)(PZA)]OTf (1, OTf = trifluoromethanesulfonate) and two gold(III) complexes [Au(PZA)Cl2] (2) and [Au(PZO)Cl2] (3, PZO = pyrazinoic acid, the metabolic product of PZA) against two mycobacteria, Mycobacterium tuberculosis and Mycobacterium smegmatis. Only complex 1 with the {Au(PPh3)}+ moiety exhibits significant bactericidal activity against both strains. In the presence of thiols, 1 gives rise to free PZA and {Au(PPh3)}-thiol polymeric species. A combination of PZA and the {Au(PPh3)}-thiol polymeric species appears to lead to enhanced efficacy of 1 against M. tuberculosis.