[Effect of seleno-organic compounds on leukotriene B4 biosynthesis].
Leukotrienes (LTs) are a group of metabolites of arachidonic acid through the 5-lipoxygenase pathway. Among these metabolites, LTB4 is an important mediator of inflammatory disease. Recently, it has been shown that seleno-organic compounds are very biologically active. One of them, Ebselen [2-phenyl-1,2-benzoisoselenazol-3 (2H) one] is a new seleno-organic compound with very low toxicity while exhibits anti-inflammatory activity. Attempt to search for seleno-organic compounds as anti-inflammatory drugs and establish structure-activity relationships, ten ebselen derivatives with modifications in the 2-phenyl moiety were studied with respect to their effects on LTB4 biosynthesis. p-substituted compounds were shown to have stronger inhibitory activity on LTB4 biosynthesis than o-substituted compounds and ebselen itself. Among the p-substituted compounds, polar-inducing group-substituted compounds showed stronger activity than compounds substituted with polar-conjugated groups. Among the compounds substituted with polar-inducing groups, strongpolar groups exhibited stronger activity than weakpolar groups.
Liu
D P
DP
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing.
Cheng
G F
GF
Bai
J Y
JY
Guo
Z R
ZR
Zhu
X Y
XY
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D054833:Isoindoles; D007962:Leukocytes / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D016566:Organoselenium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D007975:Leukotriene B4; C042986:ebselen