2-咪唑基-戊-1,4-二烯-3-酮类衍生物的合成及其抗菌活性研究  

Synthesis and evaluation of the antimicrobial activity of 2-imidazole-amyl-1,4-diene-3-ketone derivatives

作　　者：刘春丽[1] 史册[2] 刘锦燕[2] 魏冰[2] 毛斐[1] 项明洁[2,3] 李剑[1] 

机构地区：[1]华东理工大学药学院,上海200237 [2]上海交通大学医学院附属瑞金医院检验科,上海200025 [3]上海交通大学医学院附属瑞金医院卢湾分院放免检验科,上海200020

出　　处：《中国药物化学杂志》2015年第1期15-23,共9页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(21222211);上海市卫生局科研课题重点项目(20124005)

摘　　要：目的设计合成2-咪唑基-戊-1,4-二烯-3-酮类衍生物,并进行抗菌活性测试。方法以不同取代的苯甲醛为起始原料,经过Aldol缩合、溴代、亲核取代和Knoevenagel缩合四步反应合成目标化合物;采用微量稀释法测定化合物最低抑菌浓度(MIC)值。结果合成了30个未见文献报道的新化合物,其结构均经1H-NMR、MS谱测定。结论目标化合物均表现出一定的抗菌活性,可作为先导化合物做进一步改造和修饰。Bacterial infection is a kind of quite prevalent diseases. A large number of antibiotics and synthe- tic drugs are available in clinic. These drugs have been playing a vital role in the treatment of infectious di- seases. However, despite increased awareness and improved treatment strategies, the frequent development of resistance to the antibacterial drugs used in clinical settings contributes to the death of millions of people. Therefore,there is a pressing need for the discovery of new compounds with antibacterial activities. Two compounds Ia and Ib were discovered previously in our group,which exhibited good inhibitory effects on Staphylococcus aureus UA1758 and Staphylococcus epidermidis UF843 （ MIC = 8 - 32 mg·L^-1 ）. A new structural framework Ⅱ was obtained by combining Ia and lb. Then,a total of 30 derivatives（ Ⅱ 1 - Ⅱ30） of this compounds were designed, synthesized and evaluated through in vitro antibacterial activity assays. Nine compounds（ Ⅱ 1, Ⅱ3, Ⅱ9, Ⅱ 11, Ⅱ13, Ⅱ 14, Ⅱ 15, Ⅱ18, Ⅱ19 ） exhibited improved antibacterial activities against Staphylococcus epidermidis UF843 and Staphylococcus aureus UA1758 compared to the lead com- pound. Of the derivatives, compound Ⅱ 14 exhibited the strongest inhibitory effect toward Gram-positive bac- terium, With MIC value of 1 mg·L^-1. And all the compounds were invalid to Gram-negative bacterium. R^1 = CH3 , H, Br, F, OCH3 , Of2 Hs , C2 H5 , i-C3 Hv , cyclopropyl, cyclohexyl, C6 H5 ; R^2 = H, Cl, CH3 ; Ar = 4-chlorophenyl, phenyl, 4-fluorophenyl, 4-bromophenyl, 4 -methylphenyl, 2 -methylphenyl, biphenyl, 2,4 -dichlorophenyl, 4-chloro-3 -nitrophenyl, 3,4 -dichlorophenyl, 2 - furyl, 2 -thienyl, 4 -pyridyl

关 键 词：2-咪唑基-戊-1 4-二烯-3-酮 衍生物 抗菌活性 金黄色葡萄球菌 表皮葡萄球菌 

分 类 号：R914.5[医药卫生—药物化学] R96[医药卫生—药学]