Novel Consensus Docking Strategy to Improve Ligand Pose Prediction.

Molecular docking, which mainly includes pose prediction and binding affinity calculation, has become an important tool for assisting structure-based drug design. Correctly predicting the ligand binding pose to a protein target enables the estimation of binding free energy using various tools. Previous studies have shown that the consensus method can be used to improve the docking performance with respect to compound scoring and pose prediction. In this report, a novel consensus docking strategy was proposed, which uses a dynamic benchmark data set selection to determine the best program combinations to improve the docking success rate. Using the complexes from PDBbind as a benchmark data set, a 4.9% enhancement in success rate was achieved compared with the best program.

[Chemical constituents from Pteris dispar and their anti-tumor activity in vitro].

The dried whole plant of Pteris dispar were milled and extracted with 95% EtOH. The resulting dried extract was isolated by kinds of chromatographic column, including polyamide, Sephadex LH-20, preparative HPLC. As a result, ten diterpenes were isolated from the plant. By analyzing of ESI-MS and NMR spectroscopic data, the structures were established as geopyxin B(1), geopyxin E(2), ent-11α-hydroxy-18-acetoxykaur-16-ene(3), ent-14ß-hydroxy-18-acetoxykaur-16-ene(4), neolaxiflorin L(5), ent-3ß,19-dihydroxy-kaur-16-ene(6), ent-3ß-hydroxy-kaur-16-ene(7), 7ß,17-dihydroxy-16α-ent-kauran-19-oic acid 19-O-ß-D-glucopyranoside ester(8), crotonkinin C(9)and crotonkinin C(10). Compounds 1-10 were obtained from P. dispar for the first time. Compounds 1 and 2 showed moderate activities against Bel-7402 with IC50 values of 7.50 and 10.60 µmol•L⁻¹, and against HepG2 with IC50 values of 6.68,11.80 µmol•L⁻¹, respectively.

[Bioactive lignans from Silybum marianum].

The seeds of Silybum marianum were extracted by hot water, and the extract was isolated by D101 macroporous resin, MCI resin, MPLC, HPLC, et al. As a result, 7 compounds including tricin 4'-O-[threo-ß-guaiacyl-(7″-O-methyl)-glyceryl] ether(1), tricin 4'-O-[erythro-ß-guaiacyl-(7″-O-methyl)-glyceryl] ether(2), 5'-methoxyhydnocarpin-D(3),palstatin(4),(8R,7'S,8'R)-5,5'-dimethoxy-7-oxolariciresinol 9'-O-D-xylopyranoside(5), 9-O-D-glucopyranoside(6), and(-)-haplomyrtoside(7) were isolated and identified for the first time. Compounds 1, 3, 4, and 5 exhibited activity against influenza A(H5N1)with IC50 value of 0.65, 0.21, 0.32, and 0.56 µmol•L⁻¹, respectively. Compounds 1, 2, 6, and 7 exhibited cytotoxity against HepG-2 with IC50 value of 0.35, 0.25, 0.53, 0.66 µmol•L⁻¹, respectively.

[Bioactive quinolizidine alkaloids from Sophora tonkinensis].

Twelve quinolizidine alkaloids were isolated from Sophora tonkinensis by means of silica gel, preparative MPLC, and preparative HPLC. On analysis of NMR spectroscopic data, their structures were established as 3-(4-hydroxyphenyl)-4-(3-methoxy-4-hydroxyphenyl)-3,4-dehydroquinolizidine(1), lanatine A(2), cermizines C(3), senepodines G(4), senepodines H(5), jussiaeiines A(6), jussiaeiines B(7),(+)-5α-hydroxyoxysophocarpine(8),(-)-12ß-hydroxyoxysophocarpine(9),(-)-clathrotropine(10),(-)-cytisine(11), and (-)-N-methylcytisine(12), respectively. Compounds 1-7 were first isolated from Sophora L. plant. In the in vitro assays,the isolated compounds 1, 3, 6-10 exhibited potent activity against CVB3 with IC50 of 6.40, 3.25, 4.66, 3.21, 0.12, 0.23 and 1.60, and with selective index values(SI=TC50/IC50)of 12.0, 5.6, 13.0, 15.1, 50.1, 26.2, and 23.6, respectively. Compounds 1, 3, and 7 exhibited activity against staphylococcus aureus(ATCC 29213)with MICvalues of 8.0, 3.5, 6.0 g•L⁻¹, respectively. Compounds 1, 3, 7, and 12 exhibited activity against staphylococcus aureus(ATCC 33591)with MIC values of 18.0, 7.5, 8.0, 12.0 g•L⁻¹, respectively. Compounds 2, 6, 7 exhibited activity against Escherichia coli(ATCC 25922) with MIC values of 1.0, 3.2, 0.8 g•L⁻¹.