PMID- 28188798
OWN - NLM
STAT- MEDLINE
DCOM- 20170417
LR  - 20170417
IS  - 1879-0003 (Electronic)
IS  - 0141-8130 (Linking)
VI  - 98
DP  - 2017 May
TI  - In silico investigation of cycloartane triterpene derivatives from Cimicifuga 
      dahurica (Turcz.) Maxim. roots for the development of potent soluble epoxide 
      hydrolase inhibitors.
PG  - 526-534
LID - S0141-8130(16)32797-0 [pii]
LID - 10.1016/j.ijbiomac.2017.02.023 [doi]
AB  - In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, 
      we found that an ethanolic extract of the roots of Cimicifuga dahurica (Turcz.) 
      Maxim. significantly inhibits sEH in vitro. A phytochemical study on the 
      dichloromethane fraction of C. dahurica resulted in the isolation of two new 
      cycloartane triterpenoids (1 and 6), together with 13 known cycloartane analogues 
      (2-5 and 7-15). The structures of compounds were determined by spectroscopic 
      methods. All of the triterpenoid derivatives inhibited sEH enzymatic activity in 
      a concentration-dependent manner, and 13 of the tested compounds showed 
      significant activity. Among them, compounds 1, 3, 5, 7, 9, and 12 showed the 
      highest levels of inhibitory activity, with IC(50) values of about 5muM or less. 
      Kinetic analysis of compounds 1, 3, 5-9, 11, 12, and 14 revealed that compounds 
      3, 6, 7, 11, and 14 were non-competitive; 1, 5, 9, and 12 were mixed-type; and 8 
      was a competitive inhibitor. Furthermore, in silico molecular docking indicated 
      that compounds 3, 6-9, 11, 12, and 14 bound to sEH in a similar manner and had 
      stable binding energies, as calculated by AutoDock 4.2 and processed in a 
      10,000-ps molecular dynamics simulation to assess the binding stability of 
      compounds 5, 7, and 9.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Thao, Nguyen Phuong
AU  - Thao NP
AD  - College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of 
      Korea; Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and 
      Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam.
FAU - Kim, Jang Hoon
AU  - Kim JH
AD  - Korea Atomic Energy Research Institute, Jeongeup, Jeollabuk-do 580-185, Republic 
      of Korea.
FAU - Thuy Luyen, Bui Thi
AU  - Thuy Luyen BT
AD  - Department of Pharmaceutical Industry, Hanoi University of Pharmacy, 13-15 Le 
      Thanh Tong, Hanoi, Vietnam.
FAU - Dat, Nguyen Tien
AU  - Dat NT
AD  - Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and 
      Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam.
FAU - Kim, Young Ho
AU  - Kim YH
AD  - College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of 
      Korea. Electronic address: yhk@cnu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20170207
PL  - Netherlands
TA  - Int J Biol Macromol
JT  - International journal of biological macromolecules
JID - 7909578
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Triterpenes)
RN  - 511-64-8 (cycloartane)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Cimicifuga/*chemistry
MH  - *Computer Simulation
MH  - Enzyme Inhibitors/chemistry/isolation & purification/metabolism/pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors/chemistry/metabolism
MH  - Kinetics
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Plant Roots/*chemistry
MH  - Protein Domains
MH  - Solubility
MH  - Triterpenes/*chemistry/isolation & purification/metabolism/*pharmacology
OTO - NOTNLM
OT  - Cimicifuga dahurica
OT  - Cycloartane-type triterpenoids
OT  - Molecular docking
OT  - Ranunculaceae
OT  - Soluble epoxide hydrolase
EDAT- 2017/02/12 06:00
MHDA- 2017/04/18 06:00
CRDT- 2017/02/12 06:00
PHST- 2016/12/07 00:00 [received]
PHST- 2017/02/05 00:00 [revised]
PHST- 2017/02/06 00:00 [accepted]
PHST- 2017/02/12 06:00 [pubmed]
PHST- 2017/04/18 06:00 [medline]
PHST- 2017/02/12 06:00 [entrez]
AID - S0141-8130(16)32797-0 [pii]
AID - 10.1016/j.ijbiomac.2017.02.023 [doi]
PST - ppublish
SO  - Int J Biol Macromol. 2017 May;98:526-534. doi: 10.1016/j.ijbiomac.2017.02.023. 
      Epub 2017 Feb 7.