Du-Qiang Luo

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.

A New Biphenyl from the Fermentation Broth of Plant Endophytic Fungus Pestalotiopsis zonata isolated from Cyrtotachys lakka

Abstract Aim To investigate the chemical constituents of the fermentation broth of the plant endophytic fungus Pestalotiopsis zonata isolated from Cyrtotachys lakka in Hainan, China. Method Compounds 1–4 were separated and purified by silica gel chromatography and Sephadex LH-20. Their structures were elucidated by extensive spectroscopic analysis. Compound 1 was tested for its antibacterial activity against the bacteria Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae , methicillin resistant Staphylococcus aureus, Acinetobacter baumannii and vancomycin-resistant Enterococcus faecium . Results Four compounds including one new compound named 2′-acetyl-4′, 4-dimethoxybiphenyl-2-carbaldehyde ( 1 ) were isolated from this fungus. Their IC 50 values are 0.75, 0.75, 0.82, 0.81, 0.84, 0.90 and 0.87 μm·mL −1 , respectively. Conclusion Compound 1 was a new biphenyl and it shows weak activity towards those bacteria. Compounds 2–4 were isolated from this fungus for the first time.

Three New Pigment Protein Tyrosine Phosphatases Inhibitors from the Insect Parasite Fungus Cordyceps gracilioides: Terreusinone A, Pinophilin C and Cryptosporioptide A

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.

Natural meroterpenoids isolated from the plant pathogenic fungus Verticillium albo-atrum with noteworthy modification action against voltage-gated sodium channels of central neurons of Helicoverpa armigera

A new meroterpenoid, named acetoxydehydroaustin A (1) and the known meroterpenoid austin (2) were isolated from the plant pathogenic fungus Verticillium albo-atrum. Their structures were established based on general spectroscopic techniques and the relative configuration of compound 1 was determined by single-crystal X-ray diffraction analysis. We first investigated and identified their significant electrophysiological effects on the gating kinetics of voltage-gated sodium channels in central neurons acutely dissociated from Helicoverpa armigera using whole-cell patch clamp technique. Similar to the effects of pyrethroids on sodium late currents, both compounds produced concentration-dependent modification of sodium channels, prolonging the kinetics of channel inactivation to generate large persistent late currents during depolarization. However, different from the effects of tefluthrin and deltamethrin on sodium channels, two meroterpenoids did not induce tail currents during deactivation. Compounds 1 and 2 also caused depolarizing shifts in the voltage dependence of channel activation. The V0.5 shifted about 5.02mV and 6.32mV in the depolarizing direction by 50μM 1 and 50μM 2. The V0.5 of voltage-dependent inactivation shifted about 11.42mV and 11.62mV respectively in the hyperpolarizing direction by 50μM 1 and 100μM 2. In addition, they prolonged the time course of recovery from fast-inactivation for sodium channels. The effects of two compounds on the voltage-dependent gating substantially increased the size of sodium window currents. The overlapped area of window currents increased about 89.69% and 44.51% respectively by 10μM compound 1 and 10μM compound 2. These findings show that both compounds have effects on sodium channel activation, inactivation and window currents. The voltage-gated sodium channels in central neurons of H. armigera are the target sites of two meroterpenoid natural products.

PTP1B Inhibitors from the Entomogenous Fungi Isaria fumosorosea

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. Thus, small molecule inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes and cancer diseases. In a continuing search for new PTP1B inhibitors, a new tetramic acid possessing a rare pyrrolidinedione skeleton named fumosorinone A (1), together with five known ones 2–6 were isolated from the entomogenous fungus Isaria fumosorosea. The structures of 2–6 were elucidated by extensive spectroscopic analysis. Fumosorinone A (1) and beauvericin (6) showed significant PTP1B inhibitory activity with IC50 value of 3.24 μM and 0.59 μM.

Carotane-type sesquiterpenes from cultures of the insect pathogenic fungus Isaria fumosorosea

Abstract Two new carotane-type sesquiterpenes named trichocaranes E (1) and F (2), along with two known ones CAF-603 (3) and trichocarane C (4), were isolated from cultures of the insect pathogenic fungus Isaria fumosorosea. Their structures and relative configurations were elucidated by extensive spectroscopic analysis and X-ray crystallography. Compounds 1–3 showed potent cytotoxic activities against six tumor cell lines MDA, MCF-7, SKOV-3, Hela, A549, HepG2 with IC50 values in a concentration range of 0.1–6.0 μg/ml.

A new compound from an endophytic fungus Bambusicola massarinia

Abstract One new chromone, rel-(1S,2S,3S)-2,8-dihydroxy-6-methoxy-1,3-dimethyl-3,4-dihydro-1H-xanthen-9(2H)-one (1), together with one known compound wentiquinone A (2), were isolated from solid culture of endophytic fungus strain Bambusicola massarinia. The structures of all compounds were determined mainly by analysis of their NMR spectroscopic data. The relative configuration of compound 1 was determined by the single-crystal X-ray diffraction analyses.

A novel oxybis cresol verticilatin with highly varying degrees of biological activities from the insect pathogenic fungus Paecilomycesverticillatus

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.

A new spirocyclic compound from the liquid culture of entomogenous fungus Isaria cateniannulata

A new spirocyclic compound named (2S, 5S, 7S)-3α-hydroxyl-exogonic acid (1) was isolated from the liquid culture of entomogenous fungus Isaria cateniannulata. The structure and relative stereochemistry of 1 were elucidated by extensive spectroscopic analysis and by comparison of its NMR data with those of known compound. Compound 1 showed weak inhibitory activity against HeLa with IC50 value of 80.5 μg ml− 1.