Choi Ji Won, Jang Bo Ko, Cho Nam-chul, Park Jong-Hyun, Yeon Seul Ki, Ju Eun Ji, Lee Yong Sup, Han Gyoonhee, Pae Ae Nim, Kim Dong Jin, Park Ki Duk
Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, 5 Hwarang-ro, 14-gil, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, 5 Hwarang-ro, 14-gil, Seongbuk-gu, Seoul 136-791, Republic of Korea; Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Bioorg Med Chem. 2015 Oct 1;23(19):6486-96. doi: 10.1016/j.bmc.2015.08.012. Epub 2015 Aug 19.
We have synthesized three categories of α,β-unsaturated carbonyl derivatives and evaluated their MAO-A and MAO-B inhibitory activities. Among them, compound 10b including α,β-unsaturated ketone group showed the most potent and selective MAO-B inhibitory activity (IC₅₀ human MAO-B 16 nM, >6000-fold selective vs MAO-A) and compound 10b exhibited good reversibility compared with selegiline, a well-known irreversible MAO-B inhibitor. However, both α,β-unsaturated amide and ester derivatives exhibited weaker MAO-B inhibition potencies. The docking studies provided insights into the possible binding modes and the key interaction sites of the synthesized MAO-B inhibitors.
我们合成了三类α,β-不饱和羰基衍生物，并评估了它们对单胺氧化酶A（MAO-A）和单胺氧化酶B（MAO-B）的抑制活性。其中，含有α,β-不饱和酮基的化合物10b表现出最强且最具选择性的MAO-B抑制活性（人源MAO-B的IC₅₀为16 nM，对MAO-A的选择性大于6000倍），并且与著名的不可逆MAO-B抑制剂司来吉兰相比，化合物10b表现出良好的可逆性。然而，α,β-不饱和酰胺和酯衍生物对MAO-B的抑制活性较弱。对接研究为合成的MAO-B抑制剂的可能结合模式和关键相互作用位点提供了深入见解。
