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.

Sarcosenones A–C, highly oxygenated pimarane diterpenoids from an endolichenic fungus Sarcosomataceae sp.

The new highly oxygenated pimarane diterpenoids sarcosenones A–C (1–3) were isolated from an endolichenic fungus Sarcosomataceae sp. Compound 1 showed moderate cytotoxicity towards human tumor cells.