Effect of the novel non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-one on in vitro generation of some inflammatory mediators.
A newly synthesized compound, the non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne (E-5110) was investigated. E-5110 inhibited prostaglandin E2 (PGE2) generation by cultured rat synovial cells upon stimulation with interleukin-1-like factor of rat polymorphonuclear leucocytes (PMN). The IC50 values (mumol/l) for PGE2 generation were 0.026 for E-5110, 0.008 for indometacin, 0.112 for piroxicam and 0.667 for the compound B (3-amino-1-(M-trifluoromethyl-phenyl-2-pyrazoline). Calcium ionophore A23187-stimulated leukotriene B4 generation by human PMN was inhibited by E-5110 with an IC50 value of 0.20 mumol/l; E-5110 was as inhibitory as nordihydroguaiaretic acid and was more potent than the compound B (IC50 of 2.58 mumol/l). E-5110 suppressed superoxide generation by human PMN stimulated with opsonized zymosan, f-Met-Leu-Phe and phorbol myristate acetate. E-5110 also inhibited the generation of leucocytic pyrogen and leucocyte factor(s) which stimulated collagenase production by cultured synovial cells.
Shirota
H
H
Eisai Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Kobayashi
S
S
Terato
K
K
Sakuma
Y
Y
Yamada
K
K
Ikuta
H
H
Yamagishi
Y
Y
Yamatsu
I
I
Katayama
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015232:Dinoprostone; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D007375:Interleukin-1 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D010894:Piroxicam / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis; D011749:Pyrogens / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D011458:Prostaglandins E; D011749:Pyrogens; D011760:Pyrrolidinones; C054091:E 5110; D013481:Superoxides; D010894:Piroxicam; D007975:Leukotriene B4; D015232:Dinoprostone; D007213:Indomethacin