Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity.
Hypericin and pseudohypericin which have been isolated from plants of the Hypericum family are aromatic polycyclic diones. Daniel Meruelo et. al. have reported that hypericin and pseudohypericin showed potent antiretroviral activity including anti-human immunodeficiency virus (1,2). However, the mechanism of these antiretroviral activities has not been clarified. In the course of screening specific inhibitors of protein kinase C we have found that both compounds specifically inhibit protein kinase C with IC50 values 1.7 micrograms/ml and 15 micrograms/ml, respectively, and show antiproliferative activity against mammalian cells. These data suggest that antiretroviral activity of hypericin and pseudohypericin could be attributable to the inhibition of some phosphorylation involved by protein kinase C during viral infection of cells.
Takahashi
I
I
Kyowa Hakko Co., Tokyo Research Laboratories, Japan.
Nakanishi
S
S
Kobayashi
E
E
Nakano
H
H
Suzuki
K
K
Tamaoki
T
T
D000818:Animals; D000873:Anthracenes; D000998:Antiviral Agents / Q000494:pharmacology*; D001551:Benz(a)Anthracenes / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D002154:Calpain / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009206:Myocardium / Q000201:enzymology; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D012190:Retroviridae / Q000187:drug effects*
D000873:Anthracenes; D000998:Antiviral Agents; D001551:Benz(a)Anthracenes; D010569:Perylene; C004965:hypericin; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D002154:Calpain; C056602:pseudohypericin