Inhibition activities of levodopa derivatives against dopa decarboxylase / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the inhibition activities of levodopa(LD) derivatives against dopa decarboxylase(DDC). METHODS: Five compounds 1-4a/4b were synthesized and identified as 1,1-dimethyl-3-carboxyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (1), 1α-methyl-3-carboxyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline(2),3-carboxyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline(3), 1α/1α-phenyl-3-carboxyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (4a/4b). Their inhibition activities against DDC were assayed, and Michael's equation of 1 were further tested. RESULTS: Compounds 1-4 could inhibit DDC activities dose dependency, while 1 showed strongest activity with its 50% inhibition concentration to be 0.387 mmol·L-1. Compound 1 showed non-competitive inhibition model with LD against DDC enzyme. CONCLUSION: Compounds 1-4 are proved to inhibit DDC activities for the first time. Therefore, compounds 1-3 of Mucuna seeds could improve LD bioavailability effectively in part through this mechanism.