16-nor Limonoids from Harrisonia perforata as promising selective 11 beta-HSD1 inhibitors

doi:10.1038/srep36927

	16-nor Limonoids from Harrisonia perforata as promising selective 11 beta-HSD1 inhibitors
	Xiao-HuiYan 2,3; Yi, Ping 4,5; Cao, Pei 2; Yang, Shi-Ying 1,6; Fang, Xin 2; Zhang, Yu 2; Wu, Bin 2; Leng, Ying7 ; Di, Ying-Tong 2; Lv, Yang 1,6
刊名	SCIENTIFIC REPORTS
	2016-11-11
卷号	6
ISSN号	2045-2322
DOI	10.1038/srep36927
文献子类	Article
英文摘要	Two new 16-nor limonoids, harperspinoids A and B (1 and 2), with a unique 7/5/5/6/5 ring system, have been isolated from the plant Harrisonia perforate together with a known one, Harperforin G (3). Their structures were elucidated by NMR spectroscopy, X-ray diffraction analysis and computational modelling. Compound 1 exists as polymorphic crystals. Conformations of 1 in solution were further discussed based on the computational results. These compounds exhibited notable inhibitory activity against the 11 beta-HSD1 enzyme. Compound 3 had potencies for the inhibition of human 11 beta-HSD1 with high selectivity against 11 beta-HSD2 (IC50 0.58 mu M, SI > 174). Molecular docking and quantitative structure-activity relationship studies revealed a mixed regulatory mechanism.
资助项目	National Natural Science Foundation of China[21432010] ; National Natural Science Foundation of China[21372228] ; National Natural Science Foundation of China[81573323] ; National Natural Science Foundation of China[31200265] ; National Natural Science Foundation of China[31560106] ; Natural Science Foundation of Yunnan Province[2014A050] ; Technological Leading Talent Project of Yunnan Province[2015HA020] ; Central Asian Drug Discovery and Development Center of the Chinese Academy of Sciences[CAM201402] ; Central Asian Drug Discovery and Development Center of the Chinese Academy of Sciences[CAM201302] ; Xibuzhiguang Project[00000000]
WOS关键词	DEHYDROGENASE TYPE-I ; REARRANGED LIMONOIDS ; CRYSTAL-STRUCTURES ; DISCOVERY ; CHEMISTRY ; CHROMONES ; SKELETON ; TYPE-1
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000387474000001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275813]
专题	中国科学院上海药物研究所
通讯作者	Di, Ying-Tong; Lv, Yang; Hao, Xiao-Jiang
作者单位	1.Peking Union Med Coll, Beijing 100050, Peoples R China; 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Peoples R China; 3.Southwest Forestry Univ, Coll Forestry, Key Lab Forest Disaster Warning & Control Yunnan, Kunming 650224, Peoples R China; 4.Key Lab Chem Nat Prod Guizhou Prov, Guiyang 550002, Peoples R China; 5.Chinese Acad Sci, Guiyang 550002, Peoples R China; 6.Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Polymorph Drugs, Beijing 100050, Peoples R China; 7.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Xiao-HuiYan,Yi, Ping,Cao, Pei,et al. 16-nor Limonoids from Harrisonia perforata as promising selective 11 beta-HSD1 inhibitors[J]. SCIENTIFIC REPORTS,2016,6.
APA	Xiao-HuiYan.,Yi, Ping.,Cao, Pei.,Yang, Shi-Ying.,Fang, Xin.,...&Hao, Xiao-Jiang.(2016).16-nor Limonoids from Harrisonia perforata as promising selective 11 beta-HSD1 inhibitors.SCIENTIFIC REPORTS,6.
MLA	Xiao-HuiYan,et al."16-nor Limonoids from Harrisonia perforata as promising selective 11 beta-HSD1 inhibitors".SCIENTIFIC REPORTS 6(2016).