文献类型：期刊文献

英文题名：A novel dihydroxylated derivative of artemisinin from microbial transformation

作者：Zhan, Yulian[1,2];Wu, Yunshan[3,4];Xu, Fangfang[3];Bai, Yunpeng[2];Guan, Yezhi[5];Williamson, John S.[4];Liu, Bo[3,4]

机构：[1]Guilin Univ Elect Technol, Sch Life & Environm Sci, Guangxi Coll & Univ Key Lab Biomed Sensing & Inte, Guilin 541004, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]Guangzhou Univ Chinese Med, Guangdong Prov Acad Chinese Med Sci, Affiliated Hosp 2, Guangzhou 510006, Guangdong, Peoples R China;[4]Univ Mississippi, Dept Med Chem, University, MS 38677 USA;[5]Guangzhou Univ Chinese Med, Guangzhou 510006, Guangdong, Peoples R China

年份：2017

卷号：120

起止页码：93

外文期刊名：FITOTERAPIA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000407404000013)】；

基金：This work was financially supported by the National Natural Science Foundation of China (No. 81202398), Guangdong Provincial Science and Technology Project (Nos 2014A020221035, 2015A020211025, 2015B020211013, and 2016A030313646), the Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine (Nos. YN2014ZHR209 and YN2015MS03), Open Funding Project of the State Key Laboratory of Bioreactor Engineering (No. 2015OPEN16), and supported by Guangxi Colleges and Universities Key Laboratory of Biomedical Sensing and Intelligent Instrument (No. LD16119X). This work was also supported by the CDC Cooperative agreement number U01 CI000211.

语种：英文

外文关键词：Microbial transformation; Artemisinin; Cunninghamella elegans; Antimalarial drugs

摘要：Microbial transformation of artemisinin (1) by Cunninghamella elegans was investigated. Four isolated products were identified as 6 beta-hydroxyartemisinin (2), 7 alpha-hydroxyartemisinin (3), 7 beta-hydroxyartemisinin (4), and 613,7 alpha-dihydroxyartemisinin (5). The structures were elucidated by spectroscopic and X-ray crystallographic analysis. Product 5 is a novel compound and being reported here for the first time. It features two hydroxyl groups in its structure, and this is the first report on dihydroxylation of the artemisinin skeleton. Quantitative structure-activity relationship and molecular modeling studies indicate the modification of artemisinin skeleton will increase antimalarial activity and water solubility. The chemical syntheses of artemisinin derivatives at C6 or C7 position are impossible due to the lack of functional groups. 6 beta,7 alpha-Dihydroxyartemisinin is hydroxylated at both 6 beta- and 7 alpha-positions of artemisinin skeleton at the same time. Therefore, this new compound would be a good scaffold for further structural modification in the search for more potent antimalarial drugs.