Protein tyrosine phosphatase 1B inhibitors isolated from Morus bombycis.
Bioassay-guided fractionation of the chloroform-soluble fraction of Morus bombycis, using an in vitro PTP1B inhibitory assay led to the identification of three 2-arylbenzofurans, albafuran A (1), mulberrofuran W (2) and mulberrofuran D (6), along with three chalcone-derived Diels-Alder products, kuwanon J (3), kuwanon R (4), and kuwanon V (5). Compounds 1-6 showed remarkable inhibitory activity against PTP1B with IC(50) values ranging from 2.7 to 13.8 microM. Inhibition kinetics were analyzed by Lineweaver-Burk plots, which suggested that compounds 1-6 inhibited PTP1B in a mixed-type manner. The present results indicate that the respective lipophilic and hydroxyl groups of 2-arylbenzofurans and chalcone-derived Diels-Alder products play an important role in inhibition of PTP1B.
Functional Metabolite Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-333, Republic of Korea.
Duc Manh
DM
Hoang
Tran Minh
TM
Ngoc
Nguyen Tien
NT
Dat
Do Thi
do T
Ha
Young Ho
YH
Kim
Hoang Van
HV
Luong
Jong Seog
JS
Ahn
KiHwan
K
Bae
D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D031625:Morus / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001572:Benzofurans; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1