文献类型：期刊文献

英文题名：Synthesis, cytotoxicity and inhibition of NO production of ivangustin enantiomer analogues

作者：Qin, Xiang-Yang[1,4];Chen, Bing-Yang[1];Fu, Jian-Jun[2];Shan, Lei[1];Lei, Xiao-Guang[3];Zhang, Wei-Dong[1,2]

机构：[1]Second Mil Med Univ, Sch Pharm, Dept Phytochem, Shanghai 200433, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[3]Being NIBS, Natl Inst Biol Sci, Beijing 102206, Peoples R China;[4]Fourth Mil Med Univ, Sch Pharm, Dept Chem, Xian 710032, Shaanxi, Peoples R China

年份：2015

卷号：102

起止页码：256

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000361922600023)】；

基金：The work was supported by NSFC (30725045, 81202421), the Special Program for New Drug Innovation of the Ministry of Science and Technology, China (2009ZX09311-001, 2008ZX09101-Z-029, 2009ZX09103-375), National Comprehensive Technology platforms for innovative drug R&D, 2009ZX09301-007, Shanghai Leading Academic Discipline Project (B906), and in part by the Scientific Foundation of Shanghai Committee of Science and Technology (08DZ1971302, 09DZ1975700, 09DZ1971500, 09DZ1972200).

语种：英文

外文关键词：Ivangustin; Natural product analogues; Sesquiterpene lactone; Inhibition of NO production; Cytotoxicity

摘要：The eight novel ivangustin enantiomer analogues possessing alpha-methylene-gamma-butyrolactone moiety have been synthesized using (4S6R, 4S6S)-4-tert-butyldimethylsilyloxy-6-methylcyclohex-2-en-1-one (1) as starting material. These transformations were mainly carried out by aldol condensation reaction and one-pot annelation procedure. The stereochemistry of these synthesized analogues was determined by NOE analysis. Their cytoxicity was evaluated against the human cancer cell lines HCT-116 (colon), HL-60 (leukemia), QGY-7701 (liver), SMMC-7721 (liver), A549 (lung), MCF-7 (breast). The results showed that these analogues were more selective against the cell lines HL-60 and QGY-7701. Analogue 17 exhibited potent cytotoxicity and high selectivity toward HL-60 cell line with IC50 value of 1.02 mu M, which suggested that it might be a promising anti-cancer lead compound. The inhibitory activities against NO production and the cytotoxicities in RAW 264.7 macrophages were determined at the same time. All of the analogues significantly inhibited the NO production with IC50 value in the range of 3.44-6.99 mu M. Analogues 17, 22, 23 and 7 showed higher cytotoxicities, indicated their inhibitory activities against NO production may be influenced by the cytotoxicities. (C) 2015 Elsevier Masson SAS. All rights reserved.