PMID- 28472063
OWN - NLM
STAT- MEDLINE
DCOM- 20170908
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 5
DP  - 2017
TI  - Occurrence of urea-based soluble epoxide hydrolase inhibitors from the plants in 
      the order Brassicales.
PG  - e0176571
LID - 10.1371/journal.pone.0176571 [doi]
LID - e0176571
AB  - Recently, dibenzylurea-based potent soluble epoxide hydrolase (sEH) inhibitors 
      were identified in Pentadiplandra brazzeana, a plant in the order Brassicales. In 
      an effort to generalize the concept, we hypothesized that plants that produce 
      benzyl glucosinolates and corresponding isothiocyanates also produce these 
      dibenzylurea derivatives. Our overall aim here was to examine the occurrence of 
      urea derivatives in Brassicales, hoping to find biologically active urea 
      derivatives from plants. First, plants in the order Brassicales were analyzed for 
      the presence of 1, 3-dibenzylurea (compound 1), showing that three additional 
      plants in the order Brassicales produce the urea derivatives. Based on the 
      hypothesis, three dibenzylurea derivatives with sEH inhibitory activity were 
      isolated from maca (Lepidium meyenii) roots. Topical application of one of the 
      identified compounds (compound 3, human sEH IC50 = 222 nM) effectively reduced 
      pain in rat inflammatory pain model, and this compound was bioavailable after 
      oral administration in mice. The biosynthetic pathway of these urea derivatives 
      was investigated using papaya (Carica papaya) seed as a model system. Finally, a 
      small collection of plants from the Brassicales order was grown, collected, 
      extracted and screened for sEH inhibitory activity. Results show that several 
      plants of the Brassicales order could be potential sources of urea-based sEH 
      inhibitors.
FAU - Kitamura, Seiya
AU  - Kitamura S
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California Davis, Davis, California, United States of 
      America.
FAU - Morisseau, Christophe
AU  - Morisseau C
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California Davis, Davis, California, United States of 
      America.
FAU - Harris, Todd R
AU  - Harris TR
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California Davis, Davis, California, United States of 
      America.
FAU - Inceoglu, Bora
AU  - Inceoglu B
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California Davis, Davis, California, United States of 
      America.
FAU - Hammock, Bruce D
AU  - Hammock BD
AUID- ORCID: 0000-0003-1408-8317
AD  - Department of Entomology and Nematology, and UC Davis Comprehensive Cancer 
      Center, University of California Davis, Davis, California, United States of 
      America.
LA  - eng
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
PT  - Journal Article
DEP - 20170504
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Enzyme Inhibitors)
RN  - 8W8T17847W (Urea)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Animals
MH  - Brassicaceae/*chemistry
MH  - Chromatography, Liquid
MH  - Enzyme Inhibitors/chemistry/*pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors
MH  - Male
MH  - Mice
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Solubility
MH  - Spectrum Analysis/methods
MH  - Structure-Activity Relationship
MH  - Urea/*chemistry
PMC - PMC5417501
COIS- Competing Interests: The authors do not have a direct financial interest or a 
      patent directly related to material and data described in this article. 
      Nevertheless, authors BI and BDH are cofounders of Eicosis LLC, which is 
      developing a chemical sEH inhibitor for pharmacological used. Authors BI, CM and 
      BDH are coinventors on patents related to sEH inhibitors filed and owned by the 
      University of California. BDH has more than 100 patents and pending patent 
      applications on various aspects of research. An extensive list is publicly 
      available at the USPTO website. No patent has been filed related to the materials 
      described in this manuscript, nor on any closely related research. This does not 
      alter the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials.
EDAT- 2017/05/05 06:00
MHDA- 2017/09/09 06:00
PMCR- 2017/05/04
CRDT- 2017/05/05 06:00
PHST- 2016/10/24 00:00 [received]
PHST- 2017/04/12 00:00 [accepted]
PHST- 2017/05/05 06:00 [entrez]
PHST- 2017/05/05 06:00 [pubmed]
PHST- 2017/09/09 06:00 [medline]
PHST- 2017/05/04 00:00 [pmc-release]
AID - PONE-D-16-42385 [pii]
AID - 10.1371/journal.pone.0176571 [doi]
PST - epublish
SO  - PLoS One. 2017 May 4;12(5):e0176571. doi: 10.1371/journal.pone.0176571. 
      eCollection 2017.