Pyridine-containing iridium complexes as Gram-negative bacteria specific therapeutic agents with low resistance development
发布时间：2026-06-30
点击次数：
- 发布时间：
- 2026-06-30
- 影响因子：
- 3.1
- DOI码：
- 10.1016/j.jinorgbio.2026.113274
- 论文名称：
- Pyridine-containing iridium complexes as Gram-negative bacteria specific therapeutic agents with low resistance development
- 发表刊物：
- Journal of Inorganic Biochemistry
- 关键字：
- The propensity of antibiotics to provoke drug resistance in clinical applications, along with their low selectivity, has collectively contributed to the problem of antibiotic misuse, posing a major challenge in contemporary antibacterial therapy. To tackle this issue, we designed and synthesized three amphiphilic pyridine-modified iridium complexes [Ir(ppy)2(bpy-Py)]+Cl− (Irsingle bondP), [Ir(dFppy)2(bpy-Py)]+Cl− (Irsingle bondF) and [Ir(dpqx)2(bpy-Py)]+Cl− (Ir-X). All three complexes exhibited stronger bactericidal activity against Gram-negative E. coli, P. aeruginosa and A.baumannii than against Gram-positive S. aureus and E. faecalis. These three complexes selectively bound to Gram-negative pathogens over Gram-positive pathogens. Among them, Ir-X with increased lipophilicity (logP = 2.58) exhibited the most promising profile, and superior antibacterial efficacy. Mechanistic studies revealed that Ir-X combats E. coli through membrane disruption, ROS generation, and ATP depletion, collectively leading to bacterial death. In vivo experiments in a murine model of acute peritonitis demonstrated that Ir-X effectively suppresses E. coli infection without causing significant tissue damage, highlighting its potential as a therapeutic agent for treating Gram-negative bacterial infections.
- 卷号：
- 279
- 页面范围：
- 113274
- 是否译文：
- 否
- 发表时间：
- 2026-02-26
- 收录刊物：
- SCI