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

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.