title: Inhibition of protein kinase C by synthetic xanthone derivatives.
abstract: 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.
authors.affiliation: Serviço de Farmacologia, CEQOFFUP, Faculdade de Farmácia, Universidade do Porto, rua Ani;bal Cunha, 164, 4050-047, Porto, Portugal
authors.forename: Lucília
authors.initials: L
authors.lastname: Saraiva
authors.forename: Paula
authors.initials: P
authors.lastname: Fresco
authors.forename: Eugénia
authors.initials: E
authors.lastname: Pinto
authors.forename: Emília
authors.initials: E
authors.lastname: Sousa
authors.forename: Madalena
authors.initials: M
authors.lastname: Pinto
authors.forename: Jorge
authors.initials: J
authors.lastname: Gonçalves
mesh_terms: 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*
chemical_list: 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