Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang, China.
Guangxi Key Laboratory of Electrochemical and Magneto-chemical Function Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, China.
Chem Biol Drug Des. 2021 Nov;98(5):885-893. doi: 10.1111/cbdd.13943. Epub 2021 Sep 6.
The growing burden of antibiotic resistance worldwide calls for developing new classes of antimicrobial strategy. Recently years, the use of adjuvants that rescue antibiotics identified as a promising strategy for overcoming bacterial resistance. In this study, three ruthenium complexes functionalized with furan-substituted ligands(Ru(phen) (CAPIP) (Ru(Ⅱ)-1), Ru(dmp) (CAPIP) (Ru(Ⅱ)-2) and Ru(dmb) (CAPIP) (Ru(Ⅱ)-3) (dmb=4,4'-dimethyl-2,2'-bipyridine, phen=1,10-phenanthroline, dmp=2,9-dimethyl-1,10-phenanthroline, CAPIP=(E)-2- (2-(furan-2-yl)vinyl)-1H-imidazo[4,5-f][1,10]phenanthroline)) were designed and synthesized. The antimicrobial activities of all compounds against S. aureus were assessed by growth inhibition assays. The MIC values of three complexes range from 0.015 to 0.050 mg/ml. Subsequently, the Ru(II)-2 complexes which exhibited strongest antibacterial activity were further tested against bacteria biofilms formation and toxin secretion. In addition, aimed to test whether ruthenium complexes have potential value as antimicrobial adjuvants, the synergism between Ru(Ⅱ)-2 and some antibiotics against S. aureus were examined through checkerboard method. Interestingly, Ru(Ⅱ)-2 could not only effectively inhibit biofilms formation of S. aureus and inhibit the hemolysin toxin secretion, but also selectivity show synergism with two common antibiotics. More importantly, mouse infection study also verified Ru(Ⅱ)-2 were highly effective against S. aureus in vivo.
全球范围内抗生素耐药性的日益加重，需要开发新的抗菌策略。近年来，人们发现佐剂可以恢复抗生素的抗菌活性，这一策略被认为是克服细菌耐药性的一种很有前途的方法。在这项研究中，设计并合成了三种呋喃取代配体功能化的钌配合物(Ru(phen)(CAPIP)(Ru(Ⅱ)-1)、Ru(dmp)(CAPIP)(Ru(Ⅱ)-2)和Ru(dmb)(CAPIP)(Ru(Ⅱ)-3)（dmb=4,4'-二甲基-2,2'-联吡啶，phen=1,10-菲啰啉，dmp=2,9-二甲基-1,10-菲啰啉，CAPIP=(E)-2-（2-（呋喃-2-基）乙烯基）-1H-咪唑并[4,5-f][1,10]菲啰啉）。通过生长抑制实验评估了所有化合物对金黄色葡萄球菌的抗菌活性。三种配合物的 MIC 值范围为 0.015 至 0.050mg/ml。随后，进一步测试了表现出最强抗菌活性的 Ru(II)-2 配合物对细菌生物膜形成和毒素分泌的抑制作用。此外，为了测试钌配合物是否具有作为抗菌佐剂的潜力，通过棋盘法测试了 Ru(II)-2 与一些抗生素对金黄色葡萄球菌的协同作用。有趣的是，Ru(II)-2 不仅可以有效抑制金黄色葡萄球菌生物膜的形成和抑制溶血素毒素的分泌，而且对两种常见抗生素具有选择性的协同作用。更重要的是，小鼠感染研究也证实了 Ru(II)-2 在体内对金黄色葡萄球菌具有很高的疗效。
