TY - JOUR
T1 - Potent natural soluble epoxide hydrolase inhibitors from Pentadiplandra brazzeana Baillon
T2 - Synthesis, Quantification, and Measurement of Biological Activities In Vitro and In Vivo
AU - Kitamura, Seiya
AU - Morisseau, Christophe
AU - Inceoglu, Bora
AU - Kamita, Shizuo G.
AU - De Nicola, Gina R.
AU - Nyegue, Maximilienne
AU - Hammock, Bruce D.
N1 - Publisher Copyright:
© 2015 PLOS ONE.
PY - 2015/2/6
Y1 - 2015/2/6
N2 - We describe here three urea-based soluble epoxide hydrolase (sEH) inhibitors from the root of the plant Pentadiplandra brazzeana. The concentration of these ureas in the root was quantified by LC-MS/MS, showing that 1, 3-bis (4-methoxybenzyl) urea (MMU) is the most abundant (42.3 μg/g dry root weight). All of the ureas were chemically synthesized, and their inhibitory activity toward recombinant human and recombinant rat sEH was measured. The most potent compound, MMU, showed an IC50 of 92 nM via fluorescent assay and a Ki of 54 nM via radioactivity-based assay on human sEH. MMU effectively reduced inflammatory pain in a rat nociceptive pain assay. These compounds are among the most potent sEH inhibitors derived from natural sources. Moreover, inhibition of sEH by these compounds may mechanistically explain some of the therapeutic effects of P. brazzeana.
AB - We describe here three urea-based soluble epoxide hydrolase (sEH) inhibitors from the root of the plant Pentadiplandra brazzeana. The concentration of these ureas in the root was quantified by LC-MS/MS, showing that 1, 3-bis (4-methoxybenzyl) urea (MMU) is the most abundant (42.3 μg/g dry root weight). All of the ureas were chemically synthesized, and their inhibitory activity toward recombinant human and recombinant rat sEH was measured. The most potent compound, MMU, showed an IC50 of 92 nM via fluorescent assay and a Ki of 54 nM via radioactivity-based assay on human sEH. MMU effectively reduced inflammatory pain in a rat nociceptive pain assay. These compounds are among the most potent sEH inhibitors derived from natural sources. Moreover, inhibition of sEH by these compounds may mechanistically explain some of the therapeutic effects of P. brazzeana.
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U2 - 10.1371/journal.pone.0117438
DO - 10.1371/journal.pone.0117438
M3 - Article
C2 - 25659109
AN - SCOPUS:84922572660
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 2
M1 - e0117438
ER -