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本文合成4个8-位有取代基的有代表性的硬脂酰肉毒碱衍生物,并检测了它们对蛋白激酶C(PKC)的活性。与母体化合物硬脂酰肉毒碱相比,8-正丁基和8-苯基取代的衍生物在低浓度时抑制活性较低,在高浓度时抑制活性增强。8-甲基硬脂酰肉毒碱则在所测定的浓度范围内均比母体化合物抑制活性明显增强,IC_(50)为7.7μmol/L。动力学测定表明,这几个硬脂酰肉毒碱均与磷脂酰丝氨酸(PKC的磷脂辅助因子)和二油酰甘油(内源型PKC脂类活化剂)相竞争。实验结果显示8-甲基硬脂酰肉毒碱为PKC强抑制剂,预示8-甲基硬脂酸有可能成为一个抗癌制剂。
In this paper, four representative derivatives of stearoyl-carnitine substituted at the 8-position were synthesized and tested for their activity on protein kinase C (PKC). The 8-n-butyl and 8-phenyl substituted derivatives showed lower inhibitory activity at low concentrations and enhanced inhibitory activity at higher concentrations than the parent compound, stearyl carnitine. 8-methyl stearyl carnitine in the measured concentration range than the parent compound inhibitory activity was significantly enhanced, IC 50 (ET) was 7.7μmol / L. Kinetic assays showed that these stearoyl-carnitine each competed with phosphatidylserine (PKC phospholipid cofactor) and dioleoyl glycerol (endogenous PKC lipid activator). The experimental results show that 8-methyl stearyl carnitine PKK strong inhibitor, indicating that 8-methyl stearic acid may become an anti-cancer agent.