Three new pigment compounds—terreusinone A (1), pinophilin C (2) and cryptosporioptide A (3) were isolated from a solid culture of Cordyceps gracilioides. The structures of these compounds were determined by extensive spectroscopic analysis including HRESIMS, 1D- and 2D-NMR. The structure of terreusinone A (1) was further confirmed by single-crystal X-ray crystallographic diffraction analysis. In an in vitro activity assay, 1, 2 and 3 exhibited high inhibitory activity against PTP1B, SHP2, CDC25B, LAR and SHP1. Terreusinone A (1) inhibited PTP1B, SHP2, CDC25B, LAR and SHP1 enzyme with IC50 values 12.5, >50, 4.1, 10.6, 5.6 µg/mL, respectively; pinophilin C (2) with IC50 values 6.8, 8.0, 4.5, 4.7, 3.4 µg/mL, respectively; and cryptosporioptide A (3) with IC50 values 7.3, 5.7, 7.6, >50, 4.9 µg/mL, respectively.

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.

A novel oxybis cresol compound named verticilatin (1), together with two known compounds, 5-methylresorcinol (2) and 2,4-dihydroxy-3,6-dimethylbenzaldehyde (3), was isolated from cultures of the insect pathogenic fungi Paecilomyces verticillatus. The structures of compounds were determined by extensive spectroscopic analysis of HR-ESI-MS and 1D and 2D NMR including HSQC, HMBC, COSY, and ROESY. Fortunately, compound 1 exhibited significant inhibitory activities against CDC25B, cathepsin B, MEG2, and SHP2 enzyme, with IC50 values of 11.5, 3.5, 7.8, and 15 μg/ml, respectively.