文献类型：期刊文献

英文题名：Discovery of New Imidazole Derivatives Containing the 2,4-Dienone Motif with Broad-Spectrum Antifungal and Antibacterial Activity

作者：Liu, Chunliu[1];Shi, Ce[2,3];Mao, Fei[1];Xu, Yong[4];Liu, Jinyan[2];Wei, Bing[2,3];Zhu, Jin[1];Xiang, Mingjie[2,3];Li, Jian[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Radioimmunol & Clin Lab,Luwan Branch, Shanghai 200020, Peoples R China;[3]Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Lab Med, Shanghai 200025, Peoples R China;[4]Humanwell Healthcare Grp Co Ltd, Wuhan 430075, Peoples R China

年份：2014

卷号：19

期号：10

起止页码：15653

外文期刊名：MOLECULES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000344456100018)】；

基金：Financial support of this research provided by the National Natural Science Foundation of China (Grants 21222211, 21372001, 91313303), the Program for New Century Excellent Talents in University (Grant NCET-12-0853), the Fundamental Research Funds for the Central Universities is gratefully acknowledged and the Scientific Research Key Project of Shanghai Municipal Health Bureau.

语种：英文

外文关键词：imidazole; 2,4-dienone; broad-spectrum; antifungal; antibacterial

摘要：A compound containing an imidazole moiety and a 2,4-dienone motif with significant activity toward several fungi was discovered in a screen for new antifungal compounds. Then, a total of 26 derivatives of this compound were designed, synthesized and evaluated through in vitro and in vivo antifungal activity assays. Several compounds exhibited improved antifungal activities compared to the lead compound. Of the derivatives, compounds 31 and 42 exhibited strong, broad-spectrum inhibitory effects toward Candida spp. In particular, the two derivatives exhibited potent antifungal activities toward the fluconazole-resistant isolate C. albicans 64110, with both having MIC values of 8 mu g/mL. In addition, they had significant inhibitory effects toward two Gram-positive bacteria, Staphylococcus aureus UA1758 (compound 31: MIC = 8 mu g/mL; compound 42: MIC = 4 mu g/mL) and Staphylococcus epidermidis UF843 (compound 31: MIC = 8 mu g/mL; compound 42: MIC = 8 mu g/mL). The results of an animal experiment indicated that both compounds could improve the survival rate of model mice infected with ATCC 90028 (fluconazole-susceptible isolate). More importantly, the two compounds exhibited notable in vivo effects toward the fluconazole-resistant C. albicans isolate, which is promising with regard to the clinical problem posed by fluconazole-resistant Candida species.