Anti-AIDS agents--XXVI. Structure-activity correlations of gomisin-G-related anti-HIV lignans from Kadsura interior and of related synthetic analogues.
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). 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. 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.
Chen
D F
DF
Department of Pharmacognosy, Shanghai Medical University, People's Republic of China.
Zhang
S X
SX
Xie
L
L
Xie
J X
JX
Chen
K
K
Kashiwada
Y
Y
Zhou
B N
BN
Wang
P
P
Cosentino
L M
LM
Lee
K H
KH
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D014197:Trees
D019380:Anti-HIV Agents; D004365:Drugs, Chinese Herbal; D017705:Lignans