The insight of in vitro and in silico studies on cholinesterase inhibitors from the roots of Cimicifuga dahurica (Turcz.) Maxim.

Journal of Enzyme Inhibition and Medicinal Chemistry

Seo Young Yang¹  Young Ho Kim¹  Young Suk Lee¹  Yoo Kyong Han¹  Ha Van Oanh²  Bui Thi Thuy Luyen²  Nguyen Phuong Thao³  Jang Hoon Kim⁴ 

[1] College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea;Department of Pharmaceutical Industry, Hanoi University of Pharmacy, Hanoi, Vietna;Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam;Radiation Breeding Research Center, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeoungeup, Jeollabuk-do, Republic of Korea;

关键词: Cimicifuga dahurica;    Ranunculaceae;    cholinestereases inhibitor;    molecular simulation;   

DOI  :  10.1080/14756366.2018.1491847

来源: publisher

【 摘 要 】

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 IC50 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 IC50 values of 13.8 ± 1.5 and 6.5 ± 2.5 μM, and competitive with an IC50 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.

【 授权许可】

CC BY