Unique Azolyl Acylhydrazonyl Hybridization of Aloe Emodins to Access Potential Antibacterial Agents  

作　　者：Yi-Xin Wang Zhao Deng Aisha Bibi 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,Chongqing 400715,China [2]College of Pharmacy,National&Local Joint Engineering Research Center of Targeted and Innovative Therapeutics,Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine,Chongqing University of Arts and Sciences,Chongqing 402160,China

出　　处：《Chinese Journal of Chemistry》2024年第15期1741-1758,共18页中国化学（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.21971212);the Key Project of Innovation Research 2035 Pilot Plan of Southwest University(SWU-XDZD22007).

摘　　要：A type of unique azole-hybridized acylhydrazonyl aloe emodins(AAEs)were developed as new antibacterial agents for combating bacterial infections.Some target AAEs showed strong antibacterial activities,especially,tetrazolylthioether AAE 27a exhibited broad antibacterial spectrum with 16-256 folds and 8-64 folds more active antibacterial efficacy than the reference drugs aloe emodin and norfloxacin,respectively.Tetrazolylthioether AAE 27a also gave low hemolysis and cytotoxicity,as well as favorable bioavailability.Preliminary mechanism explorations revealed that tetrazolylthioether AAE 27a could cause bacterial membrane depolarization and damage the cell membrane,resulting in nucleic acid leakage.Moreover,compound 27a could intercalate into DNA to impede its replication and form supramolecular 27a-DNA gyrase complex to disturb the function of DNA gyrase.These findings would provide valuable insights for the further exploration of azolyl acylhydrazonyl aloe emodins as new potential antibacterial candidates.

关 键 词：Aloe emodin Hydrazone HETEROCYCLE ANTIBACTERIAL Membrane damage 

分 类 号：O62[理学—有机化学]