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 ...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.展开更多
A class of new potential antibacterial agents with distinctive pyrimidinone benzimidazole skeleton was developed through nucleophilic substitution and Biginelli reaction starting from urea,ethyl 4-chloroacetoacetate a...A class of new potential antibacterial agents with distinctive pyrimidinone benzimidazole skeleton was developed through nucleophilic substitution and Biginelli reaction starting from urea,ethyl 4-chloroacetoacetate and various aldehydes.Some target molecules exhibited strong antibacterial activities,especially pyrimidinone benzimidazole hybrid 9e possessed the strongest inhibitory effects on the growth of E.faecalis and P.aeruginosa with a lower MIC value of 1μg/mL than norfloxacin.Moreover,compound 9e displayed strong antibiofilm capacity,low drug resistance and excellent biosafety toward human red blood cells.Further research revealed that compound 9e could disrupt membrane integrity and cause leakage of cellular components such as proteins and nucleic acids.Meanwhile,compound 9e could decrease lactate dehydrogenase activity,block cell metabolism and interact with DNA in an intercalation manner.展开更多
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)+1 种基金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)
文摘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.
基金supported by grants from the National Natural Science Foundation of China(No.21971212)the Research Fellowship for International Young Scientists from International(Regional)-Cooperation and Exchange Program of China National Natural ScienceFoundation(No.81350110523)theKey Project of Innovation Research 2035Pilot Plan of Southwest University(SWU-XDZD22007).
文摘A class of new potential antibacterial agents with distinctive pyrimidinone benzimidazole skeleton was developed through nucleophilic substitution and Biginelli reaction starting from urea,ethyl 4-chloroacetoacetate and various aldehydes.Some target molecules exhibited strong antibacterial activities,especially pyrimidinone benzimidazole hybrid 9e possessed the strongest inhibitory effects on the growth of E.faecalis and P.aeruginosa with a lower MIC value of 1μg/mL than norfloxacin.Moreover,compound 9e displayed strong antibiofilm capacity,low drug resistance and excellent biosafety toward human red blood cells.Further research revealed that compound 9e could disrupt membrane integrity and cause leakage of cellular components such as proteins and nucleic acids.Meanwhile,compound 9e could decrease lactate dehydrogenase activity,block cell metabolism and interact with DNA in an intercalation manner.
