title: Differential in vitro anti-HIV activity of natural lignans.
abstract: 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 HIV-1.
authors.affiliation: Abteilung Angewandte Molekularbiologie, Universität Mainz, Bundesrepublik Deutschland.
authors.forename: H C
authors.initials: HC
authors.lastname: Schröder
authors.forename: H
authors.initials: H
authors.lastname: Merz
authors.forename: R
authors.initials: R
authors.lastname: Steffen
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
authors.forename: P S
authors.initials: PS
authors.lastname: Sarin
authors.forename: S
authors.initials: S
authors.lastname: Trumm
authors.forename: J
authors.initials: J
authors.lastname: Schulz
authors.forename: E
authors.initials: E
authors.lastname: Eich
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007940:Leukemia L5178; D017705:Lignans; D008031:Lignin / Q000494:pharmacology*; D051379:Mice; D010957:Plasmids; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D000998:Antiviral Agents; D017705:Lignans; D014764:Viral Proteins; D008031:Lignin; D004250:DNA Topoisomerases, Type II