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• W2912643918 endingPage "2075" @default.
• W2912643918 startingPage "2060" @default.
• W2912643918 abstract "The phytochemical study of Euphorbia prolifera led to the isolation of two tiglianes (1 and 2) and 23 mysrinanes (3–25). Most of these isolates showed significant antiadipogenic activity in 3T3-L1 adipocyte without apparent cytotoxicity. Subsequent structural modification yielded 10 derivatives, among which 1a, the 5-O-acetyl derivative of 1, turned out to be the most active compound with improved triglyceride-lowering activity (EC50 for 1 and 1a: 0.61 and 0.32 μM, respectively) and reduced cytotoxicity (selectivity index for 1 and 1a: 28 and 312, respectively). The structure–activity relationship study revealed that the trans-fused 5/7/6 ring system in an angular shape was important to the activity. A mechanistic study indicated that 1 and 1a could inhibit the glucocorticoid receptor α-Dexras1 axis in adipocyte, leading to the retardation of cell differentiation at the early stage. These findings may provide a new type of lipid-lowering agents for future antiobesity drug development." @default.
• W2912643918 created "2019-02-21" @default.
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• W2912643918 date "2019-02-01" @default.
• W2912643918 modified "2023-10-17" @default.
• W2912643918 title "Tigliane Diterpenoids as a New Type of Antiadipogenic Agents Inhibit GRα-Dexras1 Axis in Adipocytes" @default.
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• W2912643918 doi "https://doi.org/10.1021/acs.jmedchem.8b01693" @default.
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