Hypericin and pseudohypericin specifically inhibit protein kinase C: Possible relation to their antiretroviral activity

• Published in: Biochemical and biophysical research communications Vol. 165; no. 3; pp. 1207 - 1212
• Main Authors: Takahashi, Isami, Nakanishi, Satoshi, Kobayashi, Eiji, Nakano, Hirofumi, Suzuki, Kohichi, Tamaoki, Tatsuya
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 29.12.1989; Elsevier
• Subjects: AIDS/HIV; Analytical, structural and metabolic biochemistry; Animals; Antiviral Agents - pharmacology; Aromatic and heterocyclic compounds; Benz(a)Anthracenes - pharmacology; Biological and medical sciences; Brain - enzymology; Calpain - metabolism; Cattle; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Heterocyclic compounds, pigments; HIV - drug effects; Mice; Mice, Inbred BALB C; Molecular Structure; Myocardium - enzymology; Myosin-Light-Chain Kinase - antagonists & inhibitors; Other biological molecules; Perylene - analogs & derivatives; Perylene - pharmacology; Phosphorylation; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Rats; Retroviridae - drug effects; Cell culture; Protein kinase C; Guttiferae; Rodentia; Enzyme inhibitor; 3T3-Cell line; Ion exchange chromatography; Vertebrata; Mammalia; Enzymatic activity; Mouse; Cyclic compound; Dicotyledones; Angiospermae; Antiviral; Spermatophyta; Mechanism of action
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(89)92730-7

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 μg/ml and 15 μg/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.