文献类型：期刊文献

英文题名：A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens

作者：Luo, Xiao[1,2];Qian, Liujia[3,4];Xiao, Yansheng[2];Tang, Yao[2];Zhao, Yang[5];Wang, Xia[5];Gu, Luyan[2];Lei, Zuhai[2];Bao, Jianming[4];Wu, Jiahui[4];He, Tingting[2];Hu, Fupin[6];Zheng, Jing[5];Li, Honglin[5];Zhu, Weiping[1,2];Shao, Lei[4];Dong, Xiaojing[4];Chen, Daijie[3,4];Qian, Xuhong[1,2];Yang, Youjun[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[3]Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China;[4]Shanghai Inst Pharmaceut Ind, State Key Lab New Drug & Pharmaceut Proc, Shanghai 201203, Peoples R China;[5]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[6]Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200040, Peoples R China

年份：2019

卷号：10

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000455762900002)】；

基金：This work is supported by the Fundamental Research Funds for the Central Universities (No. WY1516017) and the National Natural Science Foundation of China (Nos. 21572061, 21822805, and 81573329).

语种：英文

摘要：Antimicrobial resistance is a public health emergency and warrants coordinated global efforts. Challenge is that no alternative molecular platform has been identified for discovery of abundant antimicrobial hit compounds. Xanthene libraries have been screened for bioactive compounds. However, the potentially accessible chemistry space of xanthene dyes is limited by the existing xanthene synthesis. Herein we report a mild one-step synthesis, which permits late-stage introduction of a xanthene moiety onto i.e. natural products, pharmaceuticals, and bioactive compounds and construction of a focused library of rhodamine dyes exhibiting facile functional, topographical and stereochemical diversity. In vitro screening yields 37 analogs with mid-to-high bactericidal activity against WHO priority drug-resistant pathogens. These findings suggest that synthetic dye libraries exhibiting high structural diversity is a feasible chemical space combating antibacterial resistance, to complement the natural sources.