Discovery of polypyridyl iridium(III) complexes as potent agents against resistant Candida albicans

The increasing emergence and spread of drug resistant Candida albicans represent a serious challenge for effective treatment and call for the development of new therapeutic options. To address this need, we synthesized a series of polypyridyl iridium(III) complexes and studied their antimicrobial activities. Herein, one lead iridium(III) complex Ir-3 [(ptpy)2Ir(dppz)]PF6, with ptpy = 2-(p-tolyl)pyridine and dppz = dipyrido[3,2-a:2′,3′-c]phenazine, exhibited potent and broad-spectrum antifungal activities against drug-resistant pathogens and low hemolytic activity toward mammalian cells. Furthermore, Ir-3 showed low tendency to induce resistance, displayed biofilm inhibition and eradication activities. Significantly, Ir-3 exhibited potent in vivo antifungal activity in a murine model of disseminated candidiasis. This study may pave the way for the development of novel antifungal agent based upon polypyridyl iridium(III) complex to combat antifungal resistance. [Display omitted] •Fifteen polypyridyl iridium(III) complexes [(CN)2Ir(NN)]PF6 were obtained and characterized.•Complexes [(CN)2Ir(dppz)]PF6 displayed potent in vitro fungicidal activity against drug resistant C. albicans.•Complex Ir-3 exhibited low tendency to drug resistance and showed strong against biofilm formation and eradication.•Complex Ir-3 showed potent in vivo antifungal activity in a murine model of disseminated candidiasis.