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目的考察左旋多巴衍生物对多巴脱羧酶的抑制活性分析。方法合成得到1,1二甲基-3-羧基-6,7-二羟基-1,2,3,4-四氢异喹啉(1)、1-甲基-3-羧基-6,7-二羟基-1,2,3,4-四氢异喹啉(2)、3-羧基-6,7-二羟基-1,2,3,4-四氢异喹啉(3)、1α/1β-苯基-3-羧基-6,7-二羟基-1,2,3,4-四氢异喹啉(4a/4b)5个化合物,就其对多巴脱羧酶活性的抑制作用进行测试,并测定1对多巴脱羧酶活性抑制的米氏方程参数。结果化合物1~4对多巴脱羧酶均有剂量依赖性抑制作用,其中1效果最佳,其半抑制浓度IC50为0.387 mmol·L-1,与左旋多巴对多巴脱羧酶的结合为非竞争性抑制。结论首次发现化合物1~4具有多巴脱羧酶活性抑制作用,猫豆中的化合物1~3是提高左旋多巴生物利用度的主要有效成分之一。
Objective To investigate the inhibitory activity of dopamine decarboxylase on levodopa derivatives. Synthesis of 1,1-dimethyl-3-carboxy-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (1), 1-methyl-3-carboxy-6,7 -hydroxy-1,2,3,4-tetrahydroisoquinoline (2), 3-carboxy-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (3), 1α / 1β-phenyl-3-carboxy-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (4a / 4b) were tested for their inhibitory effect on dopa decarboxylase activity The test was carried out and the Miehs equation parameters for the inhibition of the activity of dopa decarboxylase were determined. Results Compound 1 ~ 4 had a dose-dependent inhibitory effect on dopa decarboxylase, of which 1 had the best effect with IC50 of 0.387 mmol·L-1 and non-binding to dopa decarboxylase of levodopa Competitive inhibition. CONCLUSION Compounds 1 to 4 were found to have the inhibitory effect of dopa decarboxylase activity for the first time. Compounds 1 to 3 in cat bean are one of the main active ingredients for improving the bioavailability of levodopa.