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

[Image: see text] 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(PPh(3))(PZA)]OTf (1, OTf = trifluoromethanesulfonate) and two gold(III) complexes [Au(PZA)Cl(2)] (2) and [Au(PZO)Cl(2)] (3, PZO = pyrazinoic acid, the metabolic product of PZA) against two mycobacteria, Mycobacterium tuberculosis and Mycobacterium smegmatis. Only complex 1 with the {Au(PPh(3))}(+) moiety exhibits significant bactericidal activity against both strains. In the presence of thiols, 1 gives rise to free PZA and {Au(PPh(3))}-thiol polymeric species. A combination of PZA and the {Au(PPh(3))}-thiol polymeric species appears to lead to enhanced efficacy of 1 against M. tuberculosis.