A New Discovery towards Novel Skeleton of Benzimidazole-Conjugated Pyrimidinones as Unique Effective Antibacterial Agents  

作　　者：Xi Yang Rasheed Syed Bo Fang Cheng-He Zhou 

机构地区：[1]Institute of Bioorganic&Medicinal Chemistry,Key Laboratory of Applied Chemistry of Chongqing Municipality,School of Chemistry and Chemical Engineering,Southwest University,Chongqing400715,China [2]College of Pharmacy,National&Local Joint Engineering Research Center of Targeted and Innovative Therapeutics,Chongqing Key Laboratoryof KinaseModulators as InnovativeMedicine,Chongqing University of Arts and Sciences,Chongqing 402160,China

出　　处：《Chinese Journal of Chemistry》2022年第22期2642-2654,共13页中国化学（英文版）

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).

摘　　要：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.

关 键 词：PYRIMIDINONE BENZIMIDAZOLE Antibacterial Resistance Membrane 

分 类 号：O62[理学—有机化学]