Penostatin derivatives, a novel kind of protein phosphatase 1b inhibitors isolated from solid cultures of the entomogenous fungus Isaria tenuipes.
Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Therefore, small molecular inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes diseases. In a continuing search for new protein phosphatase inhibitors from fungi, we have isolated a new compound, named penostatin J (1), together with three known ones, penostatin C (2), penostatin A (3), and penostatin B (4), from cultures of the entomogenous fungus Isaria tenuipes. The structure of penostatin J (1) was elucidated by extensive spectroscopic analysis. We also demonstrate for the first time that penostatin derivatives exhibit the best PTP1B inhibitory action. These findings suggest that penostatin derivatives are a potential novel kind of PTP1B inhibitors.
College of Life Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, China.
Yu-Peng
YP
Chen
College of Life Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, China.
Chun-Gui
CG
Yang
College of Life Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, China.
Pei-Yao
PY
Wei
College of Life Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, China.
Lin
L
Li
College of Life Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002, China. duqiangluo@163.com.
Du-Qiang
DQ
Luo
New Drug Research and Development Center, North China Pharmaceutical Group Corporation, Shijiazhuang 051007, China.
Zhi-Hui
ZH
Zheng
New Drug Research and Development Center, North China Pharmaceutical Group Corporation, Shijiazhuang 051007, China.
Xin-Hua
XH
Lu
D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006999:Hypocreales / Q000187:drug effects* / Q000472:pathogenicity; D015394:Molecular Structure; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D001578:Benzopyrans; D004791:Enzyme Inhibitors; C418127:penostatin A; C517188:PPP1CB protein, human; D054645:Protein Phosphatase 1