Pimarane Diterpenoids from the Seeds of Caesalpinia minax as PTP1B Inhibitors and Insulin Sensitizers.
Protein-tyrosine phosphatase 1B (PTP1B) has been considered as a promising target for treating insulin resistance. In searching for naturally occurring PTB1B antagonists, two new pimarane diterpenoids, named 2α-hydroxy-7-oxo-pimara-8(9),15-diene (1) and 19-hydroxy-2α-acetoxy-7-oxo-pimara-8(9),15-diene (2), were isolated from the seeds of Caesalpinia minax. Their structures were determined by extensive analysis of NMR and HR-ESIMS data, and their absolute configurations were determined by electronic circular dichroism (ECD) spectra. Compound 1 was disclosed as a competitive inhibitor of PTP1B with an IC50 (the half-maximal inhibitory concentration) value of 19.44 ± 2.39 µM and a Ki (inhibition constant) value of 13.69 ± 2.72 μM. Moreover, compound 1 dose-dependently promoted insulin-stimulated glucose uptake in C2C12 myotubes through activating insulin signaling pathway. Compound 1 might be further developed as an insulin sensitizer.
['Xu|Yunshao|Y|', 'Feng|Zheling|Z|', 'Zhang|Tian|T|', 'Lv|Peng|P|', 'Cao|Jun|J|', 'Li|Dan|D|', 'Peng|Cheng|C|', 'Lin|Ligen|L|0000-0002-6799-5327']
D045784:Abietanes D000818:Animals D029911:Caesalpinia D002942:Circular Dichroism D004305:Dose-Response Relationship, Drug D004353:Drug Evaluation, Preclinical D004791:Enzyme Inhibitors D005947:Glucose D007328:Insulin D009682:Magnetic Resonance Spectroscopy D051379:Mice D015394:Molecular Structure D018485:Muscle Fibers, Skeletal D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 D012639:Seeds D021241:Spectrometry, Mass, Electrospray Ionization
pimarane diterpenoids Caesalpinia minax PTP1B glucose uptake C2C12 myotubes