2. Academic Validation
  3. Kinetics and molecular docking studies of cholinesterase inhibitors derived from water layer of Lycopodiella cernua (L.) Pic. Serm. (II)

Kinetics and molecular docking studies of cholinesterase inhibitors derived from water layer of Lycopodiella cernua (L.) Pic. Serm. (II)

  • Chem Biol Interact. 2015 Oct 5:240:74-82. doi: 10.1016/j.cbi.2015.07.008.
Tran Manh Hung 1,  Joo Sang Lee 2,  Nguyen Ngoc Chuong 3,  Jeong Ah Kim 4,  Sang Ho Oh 5,  Mi Hee Woo 2,  Jae Sue Choi 6,  Byung Sun Min 7
Affiliations

Affiliations

  • 1 College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, South Korea; Division of Pharmaceutical Chemistry, Faculty of Chemistry, University of Science, Vietnam National University-HoChiMinh City, 227 Nguyen Van Cu Street, District 5, HoChiMinh City, Viet Nam.
  • 2 College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, South Korea.
  • 3 Faculty of Traditional Medicine, HoChiMinh City University of Medicine and Pharmacy, 221B Hoang Van Thu Street, Phu Nhuan District, HoChiMinh City, Viet Nam.
  • 4 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, South Korea.
  • 5 Korean BioInformation Center (KOBIC), Daejeon 305-806, South Korea.
  • 6 Department of Food and Life Science, Pukyong National University, Busan 608-737, South Korea.
  • 7 College of Pharmacy, Drug Research and Development Center, Catholic University of Daegu, Gyeongbuk 712-702, South Korea. Electronic address: [email protected].
PMID: 26297990 DOI: 10.1016/j.cbi.2015.07.008
Abstract

Acetylcholinesterase (AChE) inhibitors increase the availability of acetylcholine in central cholinergic synapses and are the most promising drugs currently available for the treatment of Alzheimer's disease (AD). Our screening study indicated that the water fraction of the methanolic extract of Lycopodiella cernua (L.) Pic. Serm. significantly inhibited AChE in vitro. Bioassay-guided fractionation led to the isolation of a new lignan glycoside, lycocernuaside A (12), and fourteen known compounds (1-11 and 13-15). Compound 7 exhibited the most potent AChE inhibitory activity with an IC50 value of 0.23 μM. Compound 15 had the most potent inhibitory activity against BChE and BACE1 with IC50 values of 0.62 and 2.16 μM, respectively. Compounds 4 and 7 showed mixed- and competitive-type AChE inhibition. Compound 7 noncompetitively inhibited BChE whereas 15 showed competitive and 8, 13, and 14 showed mixed-type inhibition. The docking results for complexes with AChE or BChE revealed that inhibitors 4, 7, and 15 stably positioned themselves in several pocket/catalytic domains of the AChE and BChE residues.

Keywords

AChEs; Docking; Lignan glycoside; Lycopodiaceae; Lycopodiella cernua.

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