Some newly synthesized leukotriene B4 analogs inhibit LTB4-induced lysozyme release from rat polymorphonuclear leukocytes.
Antagonistic activities of newly synthesized LTB4 analogs, which possess the same olefinic geometry and the same hydroxyl group stereochemistry as natural LTB4, were investigated by studying lysozyme release from rat polymorphonuclear leukocytes (PMNLs). 14,15-Dihydro LTB4(LTB3) induced lysozyme release from PMNLs as well as LTB4, while 14,15-dehydro LTB4 did not cause lysozyme release but instead clearly inhibit LTB4-induced lysozyme release. Compounds containing aminocarbonyl groups partially retained lysozyme releasing activity. A displacement of the hydrocarbon chain at C13-20 by cyclohexenyl and beta-cyclohexylethyl groups had little effect on lysozyme release, but did strongly inhibit release induced by LTB4. These results may be useful in developing LTB4 antagonists.
Shimazaki
T
T
Department of Chemical Engineering, Tokyo Institute of Technology, Japan.
Kobayashi
Y
Y
Sato
F
F
Iwama
T
T
Shikada
K
K
D000818:Animals; D003864:Depression, Chemical; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D009113:Muramidase / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D007975:Leukotriene B4; D009113:Muramidase