title: Dammaranes from Gynostemma pentaphyllum and synthesis of their derivatives as inhibitors of protein tyrosine phosphatase 1B.
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.
authors.affiliation: Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Ji-Qing
authors.initials: JQ
authors.lastname: Xu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shen
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Hu
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D029774:Gynostemma / Q000737:chemistry; D009765:Obesity / Q000188:drug therapy*; D008517:Phytotherapy; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000037:antagonists & inhibitors; D012503:Saponins / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000097669:Dammaranes
chemical_list: D004791:Enzyme Inhibitors; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D012503:Saponins; D054852:Small Molecule Libraries; D014315:Triterpenes; D000097669:Dammaranes