Design,Synthesis and Biological Evaluation of Bengamide Analogues as ClpP Activators  

作　　者：Xue-Qing Kong Bing-Yan Wei Chen-Xi Yu Xiang Na Guan Wei-Ping Ma Gang Liu Cai-Guang Yang Fa-Jun Nan 

机构地区：[1]Chinese National Center for Drug Screening,CAS Key Laboratory of Receptor Research,Stote Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,555 Zuchongzhi Road,Shanghai 201203,China [2]University of Chinese Academy of Sciences,No.19A Yuquan Road,Beijing 100049,China [3]Yantai Key Laboratory of Nanomedicine&Advanced Preparations,Yantai Institute of Materia Medica,No.39,Science and Technology Avenue,High-tech Industrial Development Zone,Yantai,Shandong 264000,China

出　　处：《Chinese Journal of Chemistry》2020年第10期1111-1115,共5页中国化学（英文版）

基　　金：We would like to thank Hanne Ingmer for providing the strains of 8325-4,ΔclpP and ΔcpP::clpP.This work was supported by Science and Technology Commission Shanghai Municipality(16ZR1407000 and 17XD1404400);the National Natural Sci-ence Foundation of China(81861138046).

摘　　要：Summary of main observation and conclusion To combat multidrug-resistant Gram-positive bacteria,new antimicrobials particularly those with novel mechanism of action are badly needed.Different with conventional antibiotics which are typical inhibitors,small-molecule activators of bacterial CIpP represent a new class of antibiotics.No ClpP activator has been developed for clinical trial.Herein,we conducted a screening on our library of benga-mide-like ring opened analogues and found that L472-2 possesses a low minimum inhibitory concentration(MIC)against S.aureus and shows no activity for ClpP activation in vitro,but it displayed reduced antibacterial activity against S.aureus with clpP deletion.In order to obtain bengamide analogues that activate ClpP in vitro as well as possess antibacterial activity,we perform further structural modifications starting from L472-2.Compound 37 re-mains the antimicrobial activity and activation of ClpP protein in vitro,which could be viewed as a new chemical scaffold for ClpP activators and worthy of further investigation.

关 键 词：ANALOGUES ACTIVATION STARTING 

分 类 号：O62[理学—有机化学]