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

Jenny Stenger-Smith; Mireille Kamariza; Indranil Chakraborty; Ramatoulaye Ouattara; Carolyn R Bertozzi; Pradip K Mascharak

doi:10.1021/acsomega.0c00071

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

ACS Omega. 2020 Mar 18;5(12):6826-6833. doi: 10.1021/acsomega.0c00071. eCollection 2020 Mar 31.

Authors

Jenny Stenger-Smith¹, Mireille Kamariza², Indranil Chakraborty¹, Ramatoulaye Ouattara¹, Carolyn R Bertozzi², Pradip K Mascharak¹

Affiliations

¹ Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, United States.
² Department of Chemistry, Stanford University, Stanford, California 94305, United States.

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.