Anti-proliferative effect of two novel palmitoyl-carnitine analogs, selective inhibitors of protein kinase C conventional isoenzymes.

摘要: Previous studies have shown that palmitoyl-carnitine is an anti-proliferative agent and a protein kinase C inhibitor. Two new analogs were synthesized by replacing the ester bond with metabolically more stable ether bond. An LD50 value in nm range was found assays using HL-60 cells dependent on alkyl-chain length. The inhibitory action of these water-soluble compounds vitro greatly increased respect to length alkyl chain. Its effect mediated increase enzyme’s requirement for phosphatidylserine. Inhibition situ phosphorylation physiological platelet substrate phorbol ester-induced differentiation also observed. Finally, test isoenzyme selectivity, several human recombinant isoforms used. Only Ca2+-dependent classic kinase Cs (α, βΙ, βΙΙ γ) inhibited compounds, yet activities casein kinase I, Ca2+/calmodulin-dependent kinase cAMP-dependent unaffected. Thus, novel inhibitors appear be both isozyme selective. They may useful assessing individual roles cell proliferation tumor development rational candidates anti-neoplasic drug design.