Lin Shijie, Chen Yushou, Sun Yajuan, Yu Guangying, Liao Xiangwen, Yang Qiang
Department of Pharmacy, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) Haikou 570311 China.
Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science&Technology Normal University Nanchang 330013 China.
RSC Adv. 2024 May 20;14(23):16194-16206. doi: 10.1039/d4ra02152e. eCollection 2024 May 15.
The rapid emergence and spread of multidrug-resistant bacteria pose a serious challenge to human life and health, necessitating the development of novel antibacterial agents. Herein, to address this challenge, three iridium-based antibacterial agents were prepared and their antimicrobial activity were explored. Importantly, the three complexes all showed robust potency against with MIC values in the range of 1.9-7.9 μg mL. Notably, the most active complex Ir3 also exhibited relative stability in mammalian fluids and a significant antibacterial effect on clinically isolated drug-resistant bacteria. Mechanism studies further demonstrated that the complex Ir3 can kill by disrupting the integrity of the bacterial membrane and inducing ROS production. This multi-target advantage allows Ir3 to not only effectively combat bacterial resistance but also efficiently clear the bacterial biofilm. In addition, when used together, complex Ir3 could enhance the antibacterial potency of some clinical antibiotics against . Moreover, both wax worms and mouse infection model demonstrated that Ir3 has low toxicity and robust anti-infective efficacy . Overall, complex Ir3 can serve as a new antibacterial agent for combating Gram-positive bacterial infections.
多重耐药细菌的迅速出现和传播对人类生命健康构成了严峻挑战，因此需要开发新型抗菌剂。在此，为应对这一挑战，制备了三种基于铱的抗菌剂，并对其抗菌活性进行了探索。重要的是，这三种配合物对[具体细菌名称未给出]均显示出强大的抗菌效力，最低抑菌浓度（MIC）值在1.9 - 7.9 μg/mL范围内。值得注意的是，活性最高的配合物Ir3在哺乳动物体液中也表现出相对稳定性，并且对临床分离的耐药细菌具有显著的抗菌效果。机制研究进一步表明，配合物Ir3可通过破坏细菌膜的完整性并诱导活性氧（ROS）产生来杀死[具体细菌名称未给出]。这种多靶点优势使Ir3不仅能有效对抗细菌耐药性，还能高效清除细菌生物膜。此外，当与某些临床抗生素联合使用时，配合物Ir3可增强它们对[具体细菌名称未给出]的抗菌效力。而且，蜡虫和小鼠感染模型均表明Ir3毒性低且抗感染效果强。总体而言，配合物Ir3可作为一种新型抗菌剂用于对抗革兰氏阳性菌感染。
