人源和克氏锥虫脯氨酰内肽酶抑制作用的比较。

Comparison of the inhibition of human and Trypanosoma cruzi prolyl endopeptidases.

作者信息

Vendeville Sandrine, Goossens Filip, Debreu-Fontaine Marie Ange, Landry Valérie, Davioud-Charvet Elisabeth, Grellier Philippe, Scharpe Simon, Sergheraert Christian

机构信息

Institut de Biologie de Lille - Institut Pasteur de Lille, UMR CNRS 8525, Faculté de Pharmacie, Université de Lille II, 1 rue du rofesseur Calmette, BP447, 59021 cedex, Lille, France.

出版信息

Bioorg Med Chem. 2002 Jun;10(6):1719-29. doi: 10.1016/s0968-0896(02)00035-4.

DOI:10.1016/s0968-0896(02)00035-4

PMID:11937331

Abstract

Prolyl endopeptidases (PEPs) have been found in numerous species. Inhibitors of human enzyme could correct cognitive deficits in Alzheimer patients while inhibition of Trypanosoma cruzi PEP could prevent invasion phase in Chagas disease. A structure-activity relationship study carried out in a tetrahydroisoquinoline series allowed to obtain potent competitive inhibitors superior to SUAM-1221. Besides, inhibitors expected to act according to an irreversible mechanism revealed to be superior to JPT-4819, for applications linked to human enzyme inhibition.

摘要

脯氨酰内肽酶（PEP）已在众多物种中被发现。人类酶的抑制剂可纠正阿尔茨海默病患者的认知缺陷，而抑制克氏锥虫的PEP可预防恰加斯病的侵袭阶段。在四氢异喹啉系列中进行的构效关系研究使得能够获得优于SUAM - 1221的强效竞争性抑制剂。此外，预期按不可逆机制起作用的抑制剂在与人类酶抑制相关的应用中显示优于JPT - 4819。