Differential in vitro Anti-HIV Activity of Natural Lignans

• Published in: Zeitschrift für Naturforschung C. A journal of biosciences Vol. 45; no. 11; pp. 1215 - 1221
• Main Authors: Schröder, Heinz C, Merz, Helmut, Steffen, Renate, Müller, Werner E. G., Sarin, Prem S., Trumm, Susanne, Schulz, Jutta, Eich, Eckart
• Format: Journal Article
• Language: English
• Published: Germany Verlag der Zeitschrift für Naturforschung 01.12.1990
• Subjects: AIDS/HIV; Animals; Antiviral Agents - pharmacology; Cell Division - drug effects; Cell Line; DNA Topoisomerase; DNA Topoisomerases, Type II - metabolism; HIV; HIV - drug effects; HIV - physiology; HIV-1 - drug effects; HIV-1 - physiology; Humans; Leukemia L5178; Lignans; Lignin - pharmacology; Mice; Plasmids; Reverse Transcriptase; Structure-Activity Relationship; Syncytia; Viral Proteins - biosynthesis
• ISSN: 0939-5075; 1865-7125
• DOI: 10.1515/znc-1990-11-1222

Two naturally occurring lignanolides, isolated from the tropical climbing shrub Ipomoea cairica, (-)-arctigen in and (-)-trachelogen in , 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 (μм , (-)-arctigenin and (-)-trachelogenin inhibited the expression of HIV-1 proteins p 17 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/H 9) were cultivated in the presence of 0.5 μм (-)-arctigen in or 1 μм (-)-trachelogenin . At the same concentrations, the formation of syncytia in the HTLV-III B/H 9-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.