Transcriptional suppression of the HIV promoter by natural compounds.
Tannins and lignins are natural compounds contained in plants such as tea leaves. Previously, we demonstrated that tannic acid represses 12-o-tetra-decanoyl phorbol-13-acetate (TPA)-induced human immunodeficiency virus (HIV) promoter activity. Furthermore, we demonstrated that a 30-bp element located just downstream of the NF-kappaB element in the HIV promoter responds negatively to tannic acid. However, the kinds of molecules responsible for this suppressive effect have remained unknown, because tannic acid is a mixture of various galloylglucoses. Here, we examined structure-defined natural compounds for HIV promoter-suppressive effects. We found that ellagitannins suppress TPA-induced HIV promoter activity to the same extent as tannic acid. 3-phenylcoumarins, isoflavone and chalcones have more suppressive effects than ellagitannins. On the other hand, other flavonoids and acetogenins have no suppressive effect. 3-phenylcoumarins and chalcones showed no suppressive effect on the cytomegalovirus (CMV) promoter, suggesting that they act specifically on the HIV promoter. These results suggest that 3-phenylcoumarin or chalcone compounds could be used to develop novel anti-HIV drugs with an action targeted at HIV promoter activity.
Uchiumi
Fumiaki
F
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Shinjuku-ku, Tokyo 162-0826, Japan.
Hatano
Tsutomu
T
Ito
Hideyuki
H
Yoshida
Takashi
T
Tanuma
Sei-ichi
S
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D047348:Hydrolyzable Tannins; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics; D013634:Tannins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014162:Transfection
D019380:Anti-HIV Agents; D003374:Coumarins; D005419:Flavonoids; D047348:Hydrolyzable Tannins; D013634:Tannins; C013515:ellagitannin; D002599:Chalcone; D013755:Tetradecanoylphorbol Acetate