Protein tyrosine phosphatase 1B (PTP1B) inhibitorsfrom the deep-sea fungus Penicillium chrysogenum SCSIO 07007.

Three new compounds, including two new 3,4,6-trisubstituted α-pyrone derivatives, chrysopyrones A and B (1 and 2), and one new indolyl diketopiperazine derivative, penilline C (3), along with twelve known compounds (4-15), were isolated and identified from the fungus Penicillium chrysogenum SCSIO 07007, separated from deep-sea hydrothermal vent environment sample collected from the Western Atlantic. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All of the isolated compounds (1-15) were evaluated for their cytotoxic, antibacterial activities and enzyme inhibitory activities against acetylcholinesterase (AChE), α-glycosidase, and protein tyrosine phosphatase 1B (PTP1B). Among them, new compounds chrysopyrones A and B (1 and 2) displayed obvious inhibitory activities against PTP1B with IC50 values of 9.32 and 27.8 µg/mL, respectively. Furthermore, molecular docking was performed to investigate the inside perspective of the action in PTP1B enzyme.

A LC/QTOF-MS/MS application to investigate chemical compositions in a fraction with protein tyrosine phosphatase 1B inhibitory activity from Rosa rugosa flowers.

INTRODUCTION: Rosa rugosa flowers used as herbal medicine possess many activities. A fraction extracted by ethyl acetate exhibited strong inhibitive activity against protein tyrosine phosphatase 1B (PTP1B) in vitro. OBJECTIVE: Establish an efficient method of LC coupled to quadrupole time-of-flight (QTOF) with tandem MS/MS to investigate the compositions in the active fraction. METHODS: Chemical compositions were separated and investigated by LC/QTOF-MS/MS in negative electrospray ionisation (ESI) mode at different collision energy (CE) values. The maximal structural information was obtained for the identification of components. RESULTS: A total of 75 compounds including tannins, their related compounds and flavonoids were identified or partially characterised according to accurate mass and the characteristic fragments at low and high CE. Meanwhile, the fragmentation pathways of gallotannins and ellagitannins (hexahydroxydiphenoyl group and lactonised valoneoyl group) were studied and proposed and were used to trace tannins in crude extracts. CONCLUSION: The results suggest that this fraction is a source of PTP1B inhibitory activity with a potential for treating diabetes.

Chrodrimanins O-S from the fungus Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculusnudus.

Five new meroterpenoids, chrodrimanins O-S (1-5), as well as a known one (6), were isolated from the fermentation broth of Penicillium sp. SCS-KFD09 isolated from a marine worm, Sipunculusnudus, from Haikou Bay, China. The structures including the absolute configurations of the new compounds were unambiguously elucidated by spectroscopic data and ECD spectra analysis along with quantum ECD calculations. Among them, compound 1 represents the first example of an unusual trichlorinated meroterpenoid with an unique dichlorine functionality. Compounds 1 and 4-6 displayed inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 71.6, 62.5, 63.1, and 39.6µM, respectively, and showed no apparent activity against three tumor cell lines (A549, HepG2, and Hela) and human umbilical vein endothelial cells (HUVEC) at 10µM.