Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

Design, synthesis, biological evaluation and molecular dynamics simulation studies of imidazolidine-2,4-dione derivatives as novel PTP1B inhibitors.

Protein tyrosine phosphatase 1B (PTP1B) is a member of the phosphotyrosine phosphatase family and plays an important role in the signal transduction of diabetes. Inhibition of PTP1B activity can increase insulin sensitivity and reduce blood sugar levels. Therefore, it is urgent to find compounds with novel structures that can inhibit PTP1B. This study designed imidazolidine-2,4-dione derivatives through the computer-aided drug design (CADD) strategy, and the Comp#10 showed outstanding inhibitory ability. (IC50 = 2.07 µM) and selectivity. The inhibitory mechanism at molecular level of Comp#10 on PTP1B was studied by molecular dynamics simulation. The results show that the catalytic region of PTP1B protein is more stable, which makes the catalytic sites unsuitable for exposure. Interestingly, the most obvious changes in the interaction between residues in the P-loop region (such as: His214, Cys215, and Ser216). In short, this study reported for the first time that imidazolidine-2,4-dione derivatives as novel PTP1B inhibitors had good inhibitory activity and selectivity, providing new ideas for the development of small molecule PTP1B inhibitors.

The discovery of a novel and selective inhibitor of PTP1B over TCPTP: 3D QSAR pharmacophore modeling, virtual screening, synthesis, and biological evaluation.

Given the special role of insulin and leptin signaling in various biological responses, protein-tyrosine phosphatase-1B (PTP1B) was regarded as a novel therapeutic target for treating type 2 diabetes and obesity. However, owing to the highly conserved (sequence identity of about 74%) in active pocket, targeting PTP1B for drug discovery is a great challenge. In this study, we employed the software package Discovery Studio to develop 3D QSAR pharmacophore models for PTP1B and TCPTP inhibitors. It was further validated by three methods (cost analysis, test set prediction, and Fisher's test) to show that the models can be used to predict the biological activities of compounds without costly and time-consuming synthesis. The criteria for virtual screening were also validated by testing the selective PTP1B inhibitors. Virtual screening experiments and subsequent in vitro evaluation of promising hits revealed a novel and selective inhibitor of PTP1B over TCPTP. After that, a most likely binding mode was proposed. Thus, the findings reported here may provide a new strategy in discovering selective PTP1B inhibitors.

[Phenolic acid derivatives from Bauhinia glauca subsp. pernervosa].

To study the chemical constituents of Bauhinia glauca subsp. pernervosa, eleven phenolic acids were isolated from a 95% ethanol extract by using a combination of various chromatographic techniques including column chromatography over silica gel, ODS, MCI, Sephadex LH-20, and semi-preparative HPLC. By spectroscopic techniques including 1H NMR, 13C NMR, 2D NMR, and HR-ESI-MS, these compounds were identified as isopropyl O-beta-(6'-O-galloyl)-glucopyranoside (1), ethyl O-beta-(6'-O-galloyl)-glucopyranoside (2), 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-beta-D-glucopyranoside (3), 3, 4, 5-trimethoxyphenyl-beta-D-glucopyranoside (4), gallic acid (5), methyl gallate (6), ethyl gallate (7), protocatechuic acid (8), 3, 5-dimethoxy-4-hydroxybenzoic acid (9), erigeside C (10) and glucosyringic acid (11). Among them, compound 1 is a new polyhydroxyl compound; compounds 2, 10, and 11 were isolated from the genus Bauhinia for the first time, and the other compounds were isolated from the plant for the first time. Compounds 6 and 8 showed significant protein tyrosine phosphatase1B (PTP1B) inhibitory activity in vitro with the IC50 values of 72.3 and 54.1 micromol x L(-1), respectively.

[Study on biligustilides from Angelica sinensis].

OBJECTIVE: To study the chemical constituents of Angelica sinensis. METHOD: The constituents were separated by chromatographic methods, and their structures were identified on the basis of spectroscopic analysis. RESULT: Eight compounds were isolated and identified as levistolide A (1), senkyunolide O (2), (3Z, 3Z')-6.8', 7.3'-diligustilide (3), tokinolide B (4), isotokinolide B (5), (3'Z)-(3R, 8S, 3a'R, 6'S)-3, 3a': 8, 6'-biligustilide (6), E, E'-3. 3', 8. 8'-diligustilide (7) and E, E'-3. 3', 8. 8'-isodiligustilide (8), which are all diligustilides. CONCLUSION: Compound 7 was obtained from the plant for the first time; compounds 6 and 8 are new compounds.

[The megastigman glycosides from herb of Potentilla multifida].

OBJECTIVE: To investigate the chemical constituents of Potentilla multifida. METHOD: Various chromatographic techniques were employed for isolation and purification of the constituents. The structures were elucidated by spectral analysis. RESULT: Four megastigmane glycosides were isolated from P. multifida and their structures were identified as citroside A (1), icariside B1 (2), (6S,7E,9R)-roseoside (3), (6S,7E,9R)-vomifoliol-9-O-beta-D-xylopyranosyl-(1-->6)-O-beta-D-glucopyranoside (4), respectively. CONCLUSION: All compounds were obtained from the genus Potentilla for the first time.

[Isolation and identification of the ligustilide compounds from the root of Angelica sinensis].

OBJECTIVE: To find out substance basis of pharmacological activities of Angelica sinensis. METHOD: Chromatographic methods were used to isolate the chemical components, and spectroscopic methods were used to identify their structures. RESULT: Five compounds were isolated from the ethanol extract of the roots of Angelica sinensis. Their structures were identified as: (Z)-ligustilide, (Z)-6,7-epoxyligustilide, (Z)-6,7-cis-dihydroxyligustilide, (E)-6,7-cis-dihydroxy-ligustilide and 11-angeloylsenkyunolide F. CONCLUSION: 11-angeloylsenkyunolide F was obtained from Angelica sinensis for the first time.