Synthesis and in vivo modulatory activity of protein kinase C of xanthone derivatives.
The modulatory activity of a series of 20 simple xanthones on isoforms alpha, betaI, delta, eta and zeta of protein kinase C (PKC) was evaluated using an in vivo yeast phenotypic assay. Hydroxy and/or methoxyxanthones were synthesised. The majority of these compounds caused an effect compatible with activation of PKC and some showed to be more effective than the standard PKC activator (PMA or arachidonic acid). The xanthones tested differ in their efficacy and potency towards individual PKC isoforms and some showed higher selectivities for PKC-delta, -eta or -zeta, suggesting that xanthone derivatives can become valuable research tools to elucidate the physiological roles of these isoforms.
Saraiva
Lucília
L
Serviço de Farmacologia, Faculdade de Farmácia, Universidade do Porto, rua Aníbal Cunha, 164, Porto, Portugal.
Fresco
Paula
P
Pinto
Eugénia
E
Sousa
Emília
E
Pinto
Madalena
M
Gonçalves
Jorge
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics; D008322:Mammals; D011493:Protein Kinase C / Q000187:drug effects* / Q000235:genetics; D013329:Structure-Activity Relationship; D014170:Transformation, Genetic; D014966:Xanthenes / Q000138:chemical synthesis* / Q000494:pharmacology; D044004:Xanthones; D015003:Yeasts / Q000166:cytology / Q000235:genetics
D007527:Isoenzymes; D014966:Xanthenes; D044004:Xanthones; C009689:xanthone; D011493:Protein Kinase C