Z Naturforsch [C]. 1990 Nov-Dec;45(11-12):1215-21. Unique Identifier :
Two naturally occurring lignanolides, isolated from the tropical
climbing shrub Ipomoea cairica, (-)-arctigenin and (-)-trachelogenin,
were found to inhibit strongly replication of human immunodeficiency
virus type 1 (HIV-1; strain HTLV-III B) in vitro. At a concentration of
0.5 microM, (-)-arctigenin and (-)-trachelogenin inhibited the
expression of HIV-1 proteins p17 and p24 by 80-90% and 60-70%,
respectively. The reverse transcriptase activity in the culture fluids
was reduced by 80-90% when the cells (HTLV-III B/H9) were cultivated in
the presence of 0.5 microM (-)-arctigenin or 1 microM (-)-trachelogenin.
At the same concentrations, the formation of syncytia in the HTLV-III
B/H9-Jurkat cell system was inhibited by the compounds by more than 80%.
A series of other lignan type compounds displayed no anti-HIV activity.
Studying the molecular mechanism of action of (-)-arctigenin and
(-)-trachelogenin we found that both compounds are efficient inhibitors
of the nuclear matrix-associated DNA topoisomerase II activity,
particularly of the enzyme from HIV-1-infected cells. Our results
suggest that both compounds prevent the increase of topoisomerase II
activity, involved in virus replication, after infection of cells with
Animal Antiviral Agents/*PHARMACOLOGY Cell Division/DRUG EFFECTS Cell
Line Comparative Study DNA Topoisomerase (ATP-Hydrolysing)/METABOLISM
Human HIV/*DRUG EFFECTS/PHYSIOLOGY HIV-1/*DRUG EFFECTS/PHYSIOLOGY
Leukemia L5178 Lignin/*PHARMACOLOGY Mice Plasmids Structure-Activity
Relationship Support, Non-U.S. Gov't Viral Proteins/BIOSYNTHESIS