文献类型：期刊文献

英文题名：Novel Staphyloxanthin Inhibitors with Improved Potency against Multidrug Resistant Staphylococcus aureus

作者：Ni, Shuaishuai[1];Li, Baoli[1];Chen, Feifei[2];Wei, Hanwen[1];Mao, Fei[1];Liu, Yifu[1];Xu, Yixiang[1];Qiu, Xiaoxi[1];Li, Xiaokang[1];Liu, Wenwen[1];Hu, Linghao[1];Ling, Dazheng[1];Wang, Manjiong[1];Zheng, Xinyu[1];Zhu, Jin[1];Lan, Lefu[2];Li, Jian[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

年份：2018

卷号：9

期号：3

起止页码：233

外文期刊名：ACS MEDICINAL CHEMISTRY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000427331200012)】；

基金：Financial support for this research was provided by the National Key R&D Program of China (Grant 2017YFB0202600), the National Natural Science Foundation of China (Grant 21672064), the "Shu Guang" project supported by the Shanghai Municipal Education Commission, and Shanghai Education Development Foundation (Grant 14SG28). The Fundamental Research Funds for the Central Universities are gratefully acknowledged.

语种：英文

外文关键词：Virulence factor; pigment; multidrug resistant MRSA; CrtN inhibitor

摘要：Diapophytoene desaturase (CrtN) is a potential novel target for intervening in the biosynthesis of the virulence factor staphyloxanthin. In this study, 38 1,4-benzodioxan-derived CrtN inhibitors were designed and synthesized to overwhelm the defects of leading compound 4a. Derivative 47 displayed superior pigment inhibitory activity, better hERG inhibitory properties and water solubility, and significantly sensitized MRSA strains to immune clearance in vitro. Notably, 47 displayed excellent efficacy against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate MRSA, VISA), and NRS271 (linezolid-resistant MRSA, LRSA) comparable to that of linezolid and vancomycin in vivo.