title: Phainanoids A-F, a new class of potent immunosuppressive triterpenoids with an unprecedented carbon skeleton from Phyllanthus hainanensis.
abstract: Phainanoids A-F (1-6), six highly modified triterpenoids with a new carbon skeleton by incorporating two unique motifs of a 4,5- and a 5,5-spirocyclic systems, were isolated from Phyllanthus hainanensis. Their structures with absolute configurations were determined by spectroscopic data, chemical methods, and X-ray crystallography. Compounds 1-6 exhibited exceptionally potent immunosuppressive activities in vitro against the proliferation of T and B lymphocytes. The most potent one, phainanoid F (6), showed activities against the proliferation of T cells with IC50 value of 2.04 ± 0.01 nM (positive control CsA = 14.21 ± 0.01 nM) and B cells with IC50 value of <1.60 ± 0.01 nM (CsA = 352.87 ± 0.01 nM), which is about 7 and 221 times as active as CsA, respectively. The structure-activity relationships of 1-6 are discussed.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, People's Republic of China.
authors.forename: Yao-Yue
authors.initials: YY
authors.lastname: Fan
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yue
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D002244:Carbon / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D029803:Phyllanthus / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects; D014315:Triterpenes / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014315:Triterpenes; D003208:Concanavalin A; D002244:Carbon