a Radiation Breeding Research Center, Advanced Radiation Technology Institute , Korea Atomic Energy Research Institute , Jeoungeup , Jeollabuk-do , Republic of Korea.
b Institute of Marine Biochemistry (IMBC) , Vietnam Academy of Science and Technology (VAST) , Hanoi , Vietnam.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):1174-1180. doi: 10.1080/14756366.2018.1491847.
Cholinesterases (ChEs) are enzymes that break down neurotransmitters associated with cognitive function and memory. We isolated cinnamic acids (1 and 2), indolinones (3 and 4), and cycloartane triterpenoid derivatives (5-19) from the roots of Cimicifuga dahurica (Turcz.) Maxim. by chromatography. These compounds were evaluated for their inhibitory activity toward ChEs. Compound 1 was determined to have an IC value of 16.7 ± 1.9 μM, and to act as a competitive inhibitor of acetylcholinesterase (AChE). Compounds 3, 4 and 14 were found to be noncompetitive with IC values of 13.8 ± 1.5 and 6.5 ± 2.5 μM, and competitive with an IC value of 22.6 ± 0.4 μM, respectively, against butyrylcholinesterase (BuChE). Our molecular simulation suggested each key amino acid, Tyr337 of AChE and Asn228 of BuChE, which were corresponded with potential inhibitors 1, and 3 and 4, respectively. Compounds 1 and 4 were revealed to be promising compounds for inhibition of AChEs and BuChEs, respectively.
胆碱酯酶（ChE）是分解与认知功能和记忆相关的神经递质的酶。我们通过色谱法从升麻（Cimicifuga dahurica（Turcz.）Maxim.）的根部分离出肉桂酸（1 和 2）、吲哚啉酮（3 和 4）和环阿尔廷三萜衍生物（5-19）。这些化合物被评估了它们对 ChE 的抑制活性。化合物 1 的 IC 值为 16.7 ± 1.9 μM，被确定为乙酰胆碱酯酶（AChE）的竞争性抑制剂。化合物 3、4 和 14 被发现对丁酰胆碱酯酶（BuChE）具有非竞争性抑制作用，IC 值分别为 13.8 ± 1.5、6.5 ± 2.5 μM 和竞争性抑制作用，IC 值为 22.6 ± 0.4 μM。我们的分子模拟表明，每个关键氨基酸，AChE 的 Tyr337 和 BuChE 的 Asn228，分别与潜在抑制剂 1 和 3、4 相对应。化合物 1 和 4 分别被揭示为抑制 AChE 和 BuChE 的有前途的化合物。
