基于丁酸功能化基团钌化合物的合成及其抗菌活性研究  

Ruthenium Complex Based on Butyric Acid Functionalized Ligand:Synthesis and Antibacterial Activity Study

作　　者：曾威 丁云霞[1] 姜雯雯[1] 陈晓燕[1] 荣小娟 马兆霞 ZENG Wei;DING Yun-xia;JIANG Wen-wen;CHEN Xiao-yan;RONG Xiao-juan;MA Zhao-xia(School of Medicine,Jiangxi University of Technology,Nanchang,330013,China)

机构地区：[1]江西科技学院医学院,江西南昌330013

出　　处：《化学试剂》2023年第2期54-61,共8页Chemical Reagents

基　　金：江西省教育厅科技项目(GJJ202015);江西省卫健委科技计划项目(202211352)。

摘　　要：以含丁酸取代的邻菲啰啉衍生物为主配体(PHIBA)合成了两个新型抗菌钌化合物[Ru(dtb)2PHIBA](PF 6)2(Ru1)、[Ru(dmb)2PHIBA](PF 6)2(Ru2),通过最低抑菌浓度、时间杀伤曲线、溶血毒素试验、棋盘联用实验等评价了钌化合物对金黄色葡萄球菌的抗菌活性。采用DAPI/PI染色试验、(DISC 3)5膜去极化染色试验、DNA泄露试验、内膜渗透性实验及活性氧监测(DCFH-DA)试验验证了化合物Ru1的抑菌机制。最后通过大蜡螟幼虫感染模型研究了Ru1的体内抗菌活性。结果表明,两个钌配合物均具有显著的抗菌活性(MIC=1.56~6.25μg/mL),钌化合物Ru1(1.56μg/mL)能通过破坏细菌细胞膜并诱导产生ROS杀死细菌。此外,Ru1不仅能有效抑制细菌毒素的分泌,而且与部分抗生素具有协同抗菌活性(FICI≤0.5)。更为重要的是,Ru1能显著提高细菌感染后大蜡螟幼虫的存活率(40%)。研究结果表明,基于丁酸功能化配体的钌化合物具有显著的抗菌活性。Two ruthenium complexes based on butyric acid functionalized ligand:[Ru(dtb)2PHIBA](PF 6)2(Ru1),[Ru(dmb)2 PHIBA](PF 6)2(Ru2),were synthesized and characterized.Their antibacterial activity against Staphylococcus aureus were investigated through time-kill kinetics assay,rabbit erythrocyte hemolysis assays and checkerboard assay.In addition,DAPI/PI staining assay,membrane depolarization assay,DNA leakage assay and ROS generation monitored assay were employed to explore the antibacterial mechanism.At last,the antibacterial activity of Ru1 in vivo was studied using Galleria mellonella.The results indicated that two ruthenium complexes exhibited strong antibacterial activity against Staphylococcus aureus(MIC=1.56~6.25μg/mL).The most active complex Ru1(1.56μg/mL)kill bacteria through destroying bacterial cell membranes and inducing the generation of ROS.In addition,Ru1 could inhibit the toxin secretion and showing synergistic effect(FICI≤0.5)when used in combination with some antibiotics.More importantly,Ru1 also effective in vivo.In summary,ruthenium complex based on butyric acid functionalized ligand are promising antibacterial agents.

关 键 词：钌配合物 丁酸 抗菌机制 金黄色葡萄球菌 

分 类 号：R916[医药卫生—药学]