title: Canthinone alkaloids are novel protein tyrosine phosphatase 1B inhibitors.
abstract: Considerable attention has been paid to protein tyrosine phosphatase 1B (PTP1B) inhibitors as a potential therapy for diabetes. Screening of a natural compound library resulted in six canthinone alkaloids, namely, picrasidine L (1), 3,4-dimethyl-canthin-5,6-dione (2), 4-ethyl-3-methyl-canthin-5,6-dione (3), eurycomine E (4), 5-methoxy-canthin-6-one (5), and 5-acethoxy-canthin-6-one (6), as novel PTP1B inhibitors. Among these, 1 is the competitive PTP1B inhibitor with the best inhibitory selectivity between PTP1B and other PTPs and was shown to promote activity in the insulin signaling pathway in cell-based assays. Molecular docking simulations and structure-activity relationship analysis of 1 will add to its potential as a lead compound in future anti-insulin-resistant drug developments.
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan. Electronic address: liwei@phar.toho-u.ac.jp.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Higai
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Koike
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D002243:Carbolines; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Canthinone; Diabetes; Picrasidine L; Protein tyrosine phosphatase 1B