Abstract
Protein tyrosine phosphatase 1B (PTP1B) is a key factor in the negative regulation of insulin pathway and a promising target for treatment of diabetes and obesity. Herein, the sapogenin 2b, prepared from the natural triterpene saponin 1b, was modified at 3-position to establish the dammarane derivatives library via esterification, oxidation and reductive amination reaction and evaluated as PTP1B inhibitors. 3-O-para-Carboxylphenyl substituted derivative 5b was found with the best in vitro inhibition activity to protein tyrosine phosphatase 1B (IC(50)=0.27microM), where 3-O-meta-carboxylphenyl substituted 5a exhibited the best selectivity (nearly fivefolds) between PTP1B and T-cell protein tyrosine phosphatase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Dammaranes
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Diabetes Mellitus, Type 2 / drug therapy*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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Gynostemma / chemistry
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Obesity / drug therapy*
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Phytotherapy
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
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Protein Tyrosine Phosphatase, Non-Receptor Type 2 / antagonists & inhibitors
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Saponins / chemistry
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Small Molecule Libraries / chemical synthesis
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Triterpenes / chemical synthesis*
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Triterpenes / chemistry
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Triterpenes / pharmacology
Substances
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Enzyme Inhibitors
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Saponins
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Small Molecule Libraries
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Triterpenes
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatase, Non-Receptor Type 2