Discovery of polypyridyl iridium(III) complexes as potent agents against resistant Candida albicans
Discovery of polypyridyl iridium(III) complexes as potent agents against resistant Candida albicans
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DOI：
10.1016/j.ejmech.2022.114250
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发表时间：
2022-03-09
影响因子：
6.7
通讯作者：
Liao, Guojian
中科院分区：
文献类型：
--
作者：
Fu, Chen;Lv, Qian;Liao, Guojian
耐药白色念珠菌的不断出现和传播对有效治疗提出了严峻挑战，并要求开发新的治疗方案。为了满足这一需求，我们合成了一系列多吡啶铱（III）配合物，并研究了它们的抗菌活性。本文报道了一种铅铱配合物Ir-3 [（ptpy）2 Ir（dppz）] PF 6（其中ptpy = 2-（对甲苯基）吡啶，dppz =联吡啶并[3，2-a：2 '，3'-c]吩嗪）对耐药病原体表现出有效的广谱抗真菌活性，对哺乳动物细胞表现出低溶血活性。此外，Ir-3表现出较低的诱导抗性的倾向，显示生物膜抑制和根除活性。值得注意的是，Ir-3在播散性念珠菌病的小鼠模型中表现出有效的体内抗真菌活性。本研究为基于多吡啶铱（III）配合物的新型抗真菌药物的开发铺平了道路。(c)2022 Elsevier Masson SAS。All rights reserved.
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. (c) 2022 Elsevier Masson SAS. All rights reserved.