Design,synthesis,and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs  

作　　者：ZHANG HuiZhen LIN JianMei RASHEED Syed ZHOU ChengHe 

机构地区：[1]School of Chemistry and Chemical Engineering,Southwest University [2]Sichuan Provincial People's Hospital

出　　处：《Science China Chemistry》2014年第6期807-822,共16页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China (21172181,21372186);the Research Fellowship for International Young Scientists from the International (Regional) Cooperation and Exchange Program (81250110554,81350110338,81350110523);the key program from Natural Science Foundation of Chongqing (CSTC2012- jjB10026);the Specialized Research Fund for the Doctoral Program of Higher Education of China (20110182110007)

摘　　要：A series of new benzimidazole derivatives was synthesized and characterized by IR,1H NMR,13C NMR,MS,and HRMS spectra.All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique.The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin,Norfloxacin,and Fluconazole.The combination of2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin,Norfloxacin,and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A.flavus.In addition,the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.A series of new benzimidazole derivatives was synthesized and characterized by IR,1H NMR,13C NMR,MS,and HRMS spectra.All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique.The bioactive evaluation showed that 3,5-bis（trifluoromethyl）phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin,Norfloxacin,and Fluconazole.The combination of2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin,Norfloxacin,and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A.flavus.In addition,the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.

关 键 词：BENZIMIDAZOLE ANTIBACTERIAL ANTIFUNGAL calf thymus DNA synergistic effect 

分 类 号：TQ465[化学工程—制药化工]