The World Health Organization has named the resistance of microbes to known antimicrobial drugs a great threat to humans and the economy.[1] In the United States alone, each year at least 2,049,442 infections and 23,000 deaths are accounted to resistant microbes.[2] Global alliances to conquer antibiotic resistance have been formed, and the need for new antimicrobial agents is undisputed.[3] The antimicrobial properties of copper and gallium have been widely investigated, leading to Greek mythology comparisons for their mechanism of action: Cu2+ the Achilles heel of M. tuberculosis,[4] and Ga3+ the Trojan horse subterfuge for Fe3+.[5] In a coordination chemistry approach to new potential metalloantimicrobials, our group has synthesized gallium(III) and iron(III) complexes of the (fluoro-)quinolones, a class of synthetic broad-spectrum antibiotics. In addition, we have worked on modified quinolone ligands, which we have coordinated to copper(II). Syntheses and characterization data of these complexes will be presented together with the results of antimicrobial susceptibility studies on Gram-positive and Gram-negative bacteria and ESKAPE pathogens. [1] World Health Organization (WHO), Antimicrobial resistance: Global report on surveillance, June 2014, Geneva, Switzerland. [2] U.S. Department of Health and Human Services, Centers for Disease Control and Prevention: Antibiotic resistance threats in the United States 2013, September 2013, Atlanta, GA. [3] Infectious Diseases Society of America Clin. Infect. Dis. 2010, 50, 1081 and Clin. Infect. Dis. 2013, doi: 10.1093/cid/cit152. [4] Wolschendorf, F.; Ackart, D.; Shrestha, T.B.; Hascall-Dove, L.; Nolan, S.; Lamichhane, G.; Wang, Y.; Bossmann, S.H.; Basaraba, R.J.; Niederweiss, M. Procl. Natl. Acad. Sci. USA 2011, 108, 1621. [5] Kaneko, Y.; Thoendel, M.; Olakanmi, O.; Britigan, B.E., Singh, P.K. J. Clin. Invest. 2007, 117, 877.

Trojan horse and Achilles heel: Can coordination complexes of Ga3+ and Cu2+ fight bacterial resistance, or is it Greek mythology?

249th National Meeting (2015)

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