PMID- 27435571
OWN - NLM
STAT- MEDLINE
DCOM- 20170928
LR  - 20170928
IS  - 1366-5928 (Electronic)
IS  - 0049-8254 (Linking)
VI  - 47
IP  - 6
DP  - 2017 Jun
TI  - Inhibition of human catechol-O-methyltransferase-mediated dopamine O-methylation 
      by daphnetin and its Phase II metabolites.
PG  - 498-504
LID - 10.1080/00498254.2016.1204567 [doi]
AB  - 1. Finding and developing inhibitors of catechol-O-methyltransferase (COMT) from 
      natural products is highly recommended. Daphnetin, a naturally occurring catechol 
      from the family thymelaeaceae, has a chemical structure similar to several potent 
      COMT inhibitors reported previously. Here the potential of daphnetin and its 
      Phase II metabolites as inhibitors of COMT was investigated with human liver 
      cytosol (HLC). 2. Daphnetin and its methylated metabolite (8-O-methyldaphnetin) 
      were found to inhibit COMT-mediated dopamine O-methylation in a dose-dependent 
      manner. The IC(50) values for daphnetin (0.51 approximately 0.53 muM) and 8-O-methyldaphnetin 
      (22.5 approximately 24.3 muM) were little affected by changes in HLC concentrations. Further 
      kinetic analysis showed the differences in inhibition type and parameters (K(i)) 
      between daphnetin (competitive, 0.37 muM) and 8-O-methyldaphnetin (noncompetitive, 
      25.7 muM). Other metabolites, including glucuronidated and sulfated species, 
      showed negligible inhibition against COMT. By using in vitro-in vivo 
      extrapolation (IV-IVE), a 24.3-fold increase in the exposure of the COMT 
      substrates was predicted when they are co-administrated with daphnetin. 3. With 
      high COMT-inhibiting activity, daphnetin could serve as a lead compound for the 
      design and development of new COMT inhibitors. Also, much attention should be 
      paid to the clinical impact of combination of daphnetin and herbal preparations 
      containing daphnetin with the drugs primarily cleared by COMT.
FAU - Liang, Si-Cheng
AU  - Liang SC
AD  - a Laboratory of Pharmaceutical Resource Discovery , Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences , Dalian , China.
AD  - b Second Affiliated Hospital of Dalian Medical University , Dalian , China.
AD  - c Graduate University of Chinese Academy of Sciences , Beijing , China , and.
FAU - Ge, Guang-Bo
AU  - Ge GB
AD  - a Laboratory of Pharmaceutical Resource Discovery , Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences , Dalian , China.
FAU - Xia, Yang-Liu
AU  - Xia YL
AD  - a Laboratory of Pharmaceutical Resource Discovery , Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences , Dalian , China.
FAU - Pei-Pei, Dong
AU  - Pei-Pei D
AD  - d College of Pharmacy, Dalian Medical University , Dalian , China.
FAU - Ping, Wang
AU  - Ping W
AD  - a Laboratory of Pharmaceutical Resource Discovery , Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences , Dalian , China.
FAU - Qi, Xiao-Yi
AU  - Qi XY
AD  - a Laboratory of Pharmaceutical Resource Discovery , Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences , Dalian , China.
AD  - b Second Affiliated Hospital of Dalian Medical University , Dalian , China.
FAU - Cai-Xia, Tu
AU  - Cai-Xia T
AD  - b Second Affiliated Hospital of Dalian Medical University , Dalian , China.
FAU - Ling, Yang
AU  - Ling Y
AD  - a Laboratory of Pharmaceutical Resource Discovery , Dalian Institute of Chemical 
      Physics, Chinese Academy of Sciences , Dalian , China.
LA  - eng
PT  - Journal Article
DEP - 20160720
PL  - England
TA  - Xenobiotica
JT  - Xenobiotica; the fate of foreign compounds in biological systems
JID - 1306665
RN  - 0 (Catechol O-Methyltransferase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Umbelliferones)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
RN  - VTD58H1Z2X (Dopamine)
RN  - XC84571RD2 (daphnetin)
SB  - IM
MH  - Catechol O-Methyltransferase/*metabolism
MH  - Catechol O-Methyltransferase Inhibitors/metabolism/*pharmacology
MH  - Dopamine
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Kinetics
MH  - Metabolic Detoxication, Phase II
MH  - Methylation
MH  - Umbelliferones/metabolism/*pharmacology
OTO - NOTNLM
OT  - 8-O-methyldaphnetin
OT  - COMT inhibitor
OT  - Daphnetin
OT  - Phase II metabolite
OT  - ligand-protein interaction
OT  - structural modification
EDAT- 2016/07/21 06:00
MHDA- 2017/09/29 06:00
CRDT- 2016/07/21 06:00
PHST- 2016/07/21 06:00 [pubmed]
PHST- 2017/09/29 06:00 [medline]
PHST- 2016/07/21 06:00 [entrez]
AID - 10.1080/00498254.2016.1204567 [doi]
PST - ppublish
SO  - Xenobiotica. 2017 Jun;47(6):498-504. doi: 10.1080/00498254.2016.1204567. Epub 
      2016 Jul 20.