title: In vitro effects of cinnamic acid derivatives on protein tyrosine phosphatase 1B.
abstract: Protein Tyrosine Phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling pathways. Finding selective PTP1B inhibitors from natural sources has been widely recognized as a potential drug target for the treatment of diabetes mellitus and obesity. In the present study, we evaluated the inhibitory activity of cinnamic acid derivatives against PTP1B in vitro. Among 14 cinnamic acid derivatives and related compounds, the most potent inhibitor PTP1Bs were o-hydroxycinnamic acid and p-hydroxycinnamic acid, which had IC50 values of 137.67 ± 13.37 and 181.60 ± 9.34 µM, respectively. The kinetics analysis revealed that PTP1B was inhibited by o-hydroxycinnamic acid and p-hydroxycinnamic acid in a non-competitive manner. o-Hydroxycinnamic acid (25 μM) and p-hydroxycinnamic acid (25 μM), in combination with sodium orthovanadate (0.0125 μM), demonstrated a synergistic effect to inhibit PTP1B activity. In conclusion, the findings provide a new insight into naturally occurring PTP1B inhibitors that could be useful for treatment of diabetes and obesity.
authors.affiliation: Department of Nutrition and Dietetics, Faculty of Allied Health Sciences, The Medical Food Research and Development Center, Chulalongkorn University , Bangkok , Thailand.
authors.forename: Sirichai
authors.initials: S
authors.lastname: Adisakwattana
authors.forename: Jirawan
authors.initials: J
authors.lastname: Pongsuwan
authors.forename: Chompunut
authors.initials: C
authors.lastname: Wungcharoen
authors.forename: Sirintorn
authors.initials: S
authors.lastname: Yibchok-anun
mesh_terms: D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002934:Cinnamates; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C029010:cinnamic acid; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1