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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / drug effects
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Carbon / chemistry*
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Concanavalin A / antagonists & inhibitors
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Concanavalin A / pharmacology
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Immunosuppressive Agents / chemistry*
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Immunosuppressive Agents / isolation & purification*
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Immunosuppressive Agents / pharmacology
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Mice
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Models, Molecular
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Molecular Conformation
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Phyllanthus / chemistry*
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Stereoisomerism
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Structure-Activity Relationship
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T-Lymphocytes / drug effects
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Triterpenes / chemistry*
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Triterpenes / isolation & purification*
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Triterpenes / pharmacology
Substances
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Immunosuppressive Agents
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Lipopolysaccharides
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Triterpenes
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Concanavalin A
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Carbon