Inhibition of protein kinase C by synthetic xanthone derivatives.
The modulatory activity of two xanthones (3,4-dihydroxyxanthone and 1-formyl-4-hydroxy-3-methoxyxanthone) on isoforms alpha, betaI, delta, eta and zeta of protein kinase C (PKC) was evaluated using an in vivo yeast phenotypic assay. Both xanthones caused an effect compatible with PKC inhibition, similar to that elicited by known PKC inhibitors (chelerythrine and NPC 15437). PKC inhibition caused by xanthones was confirmed using an in vitro kinase assay. The yeast phenotypic assay revealed that xanthones present differences on their potency towards the distinct PKC isoforms tested. It is concluded that 3,4-dihydroxyxanthone and 1-formyl-4-hydroxy-3-methoxyxanthone may become useful PKC inhibitors and xanthone derivatives can be explored to develop new isoform-selective PKC inhibitors.
Saraiva
Lucília
L
Serviço de Farmacologia, CEQOFFUP, Faculdade de Farmácia, Universidade do Porto, rua Ani;bal Cunha, 164, 4050-047, Porto, Portugal
Fresco
Paula
P
Pinto
Eugénia
E
Sousa
Emília
E
Pinto
Madalena
M
Gonçalves
Jorge
J
D000470:Alkaloids; D016718:Arachidonic Acid / Q000378:metabolism; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015151:Immunoblotting; D007120:Immunochemistry; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D010617:Phenanthridines / Q000494:pharmacology; D010641:Phenotype; D010718:Phosphatidylserines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014970:Xanthines / Q000138:chemical synthesis* / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007527:Isoenzymes; D010617:Phenanthridines; D010718:Phosphatidylserines; D010880:Piperidines; D014970:Xanthines; C069701:NPC 15437; D016718:Arachidonic Acid; C016299:chelerythrine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate