文献类型：期刊文献

英文题名：Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo

作者：Ni, Shuaishuai[1];Wei, Hanwen[1];Li, Baoli[1];Chen, Feifei[2];Liu, Yifu[1];Chen, Wenhua[1];Xu, Yixiang[1];Qiu, Xiaoxia[1];Li, Xiaokang[1];Lu, Yanli[1];Liu, Wenwen[1];Hu, Linhao[1];Lin, Dazheng[1];Wang, Manjiong[1];Zheng, Xinyu[1];Mao, Fei[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：2017

卷号：60

期号：19

起止页码：8145

外文期刊名：JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000413131400014)】；

基金：Financial support for this research provided by the National Natural Science Foundation of China (Grant 21672064), the National Key R&D Program of China (Grant 2017YFB0-202600), the "Shu Guang" project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation (Grant 14SG28), and the Fundamental Research Funds for the Central Universities is gratefully acknowledged.

语种：英文

摘要：Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831-4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.