| In vitro: |
| Bioorg Med Chem. 1997 Aug;5(8):1715-23. | | Anti-AIDS agents--XXVI. Structure-activity correlations of gomisin-G-related anti-HIV lignans from Kadsura interior and of related synthetic analogues.[Pubmed: 9313872] | Bioactivity-directed fractionation of an ethanolic extract of the stems of Kadsura interior led to the isolation and identification of 12 known lignans (1-12).
METHODS AND RESULTS:
Seven of these compounds (1, 6, 8-12) were active as anti-HIV agents. Gomisin G (11) exhibited the most potent anti-HIV activity with EC50 and therapeutic index (TI) values of 0.006 microgram/mL and 300, respectively. Schisantherin-D (6), kadsuranin (8), and schisandrin-C (10) showed good activity with EC50 values of 0.5, 0.8, and 1.2 micrograms/mL, and TI values of 110, 56, and 33.3, respectively. Ten related synthetic biphenyl compounds, five variously substituted bismethylenedioxy, dimethoxy, and dimethoxycarbonyl isomers (18-22) and five brominated derivatives (23-27) also were evaluated for inhibitory activity against HIV-1 replication in acutely infected H9 cells. The total syntheses of two new isomers (21 and 22) are reported for the first time.
CONCLUSIONS:
The anti-HIV data indicated that the relative position and types of substituents on the phenolic hydroxy groups of either the natural lignans or the synthetic biphenyl compounds rather than the numbers of bromine(s) on the aromatic rings are of primary importance. In the cyclooctane ring of the natural lignans, the position and substitution of hydroxy groups are also important to enhanced anti-HIV activity. | | Lat. Am. J. Pharm., 2016,35 (1): 192-4. | | In silico application in the prediction of herb-drug interaction for cerebrovascular diseases herbs[Reference: WebLink] |
Herb-drug interaction remains to be a key factor limiting the clinical application of drugs and herbs.
METHODS AND RESULTS:
In the present study, in silico method was used to predict herb-drug interaction for cerebrovascular diseases herbal ingredient picroside-III. The crystal structure of cytochrome P450 (CYP) 3A4 was determined with ketoconazole, available in the protein data bank with the entry code 2V0M. The structures of picroside-III was drawn using ChemDraw Ultra 8.0 and the minimization of energy was performed with Chem3D Ultra 8.0. All the docking process was performed using autodock software. Before docking of Gomisin G into the active cavity of CYP3A4, the ligand ketoconazole was firstly extracted from the binding site, and then picroside-III was docked into the binding cavity of CYP3A4. Picroside-III exerted strong interaction with amino acids residues Phe213 and Glu374. Relatively far distance exists between picroside-III and iron in the catalytic center of CYP3A4. When picroside-III was co-administered with the inhibitor ligand ketoconazole into the activity cavity of CYP3A4, we found no significant overlapping area for the binding of picroside-III and ketoconazole towards the activity center of CYP3A4.
CONCLUSIONS:
All the results indicated the little possibility for the drug-drug interaction between picroside-III and substrates and inhibitors of CYP3A4. |
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