Cyclometalated iridium(III) complexes combined with fluconazole: antifungal activity against resistant C. albicans

Front Cell Infect Microbiol. 2023 Jul 21:13:1200747. doi: 10.3389/fcimb.2023.1200747. eCollection 2023.

Abstract

Candida albicans (C. albicans) is a ubiquitous clinical fungal pathogen. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. In this study, we synthesized a series of cyclometalated iridium(III) complexes with the formula [Ir(C-N)2(tpphz)](PF6) (C-N = 2-phenylpyridine (ppy, in Ir1), 2-(2-thienyl)pyridine (thpy, in Ir2), 2-(2,4-difluorophenyl) pyridine (dfppy, in Ir3), tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) and polypyridyl ruthenium(II) complexes with the formula [Ru(N-N)2(tpphz)](PF6)2 (N-N = 2,2'-bipyridine (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3)), and investigated their antifungal activities against drug-resistant C. albicans and their combination with fluconazole (FLC). Of which, the combination of the lead iridium(III) complex Ir2 and FLC showed strong antifungal activity against drug-resistant C. albicans. Mechanism studies have shown that they can inhibit the formation of hyphae and biofilm, damage mitochondrial function and accumulate intracellular ROS. Therefore, iridium(III) complexes combined with FLC can be used as a promising treatment to exert anti-drug-resistant C. albicans activity, in order to improve the treatment efficiency of fungal infection.

Keywords: C. albicans; ROS; antifungal activity; fluconazole; iridium(III) complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents* / pharmacology
  • Candida albicans
  • Fluconazole* / pharmacology
  • Iridium / pharmacology
  • Pyridines / pharmacology

Substances

  • Fluconazole
  • Antifungal Agents
  • Iridium
  • Pyridines

Grants and funding

We thank the National Natural Science Foundation of China (22007042, 21967014), Applied Basic Research Projects of Yunnan Province (202001AT070036), Yunnan Province Science and Technology Department (202101AF070001, 202103AC100005), High-level Scientific Research Foundation for Talent Introduction of Kunming University of Science and Technology (KKKP201826008).