title: JJK694, a synthesized obovatol derivative, inhibits platelet activation by suppressing cyclooxygenase and lipoxygenase activities.
abstract: Obovatol has various biological activities, including anti-proliferative, neurotrophic, anti-fibrillogenic, anti-platelet, anti-fungal and anti-inflammatory activities. In this study, we investigated the effects of JJK694, a synthesized obovatol derivative, on rabbit platelet activation and its molecular mechanisms. JJK694 significantly inhibited washed rabbit platelet aggregation and serotonin secretion induced by collagen and arachidonic acid, but had little effect on thrombin- or U46619-induced aggregation. These results suggest that JJK694 selectively inhibits collagen- and arachidonic acid-mediated signaling. JJK694 also showed a concentration-dependent decrease in cytosolic Ca(2+) mobilization, but it had no effect on arachidonic acid liberation. On the other hand, it significantly inhibited the formation of arachidonic acid metabolites, including thromboxane A(2) (TXA(2)), prostaglandin D(2), and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), by suppression of cyclooxygenase (COX)-1 and lipoxygenase (LOX) activities. These results indicate that JJK694 hasanti-platelet activities through inhibition of arachidonic acid metabolite production by suppression of COX-1 and LOX activities.
authors.affiliation: Laboratory for Chemical Genomics, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Yu
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Yong-Ki
authors.initials: YK
authors.lastname: Min
authors.forename: Tack-Joong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
authors.forename: Mi-Yea
authors.initials: MY
authors.lastname: Lee
authors.forename: Yeo-Pyo
authors.initials: YP
authors.lastname: Yun
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000096:biosynthesis; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism
chemical_list: C581089:5-propyl-3-(4-propylphenoxy)benzene-1,2-diol; D001713:Biphenyl Compounds; D002396:Catechols; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; D010975:Platelet Aggregation Inhibitors; D012701:Serotonin; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C036795:obovatol; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D002118:Calcium