[Inhibitory effects of benzoisoselenothiazolidone sulfonamide derivatives on cyclooxygenase].
OBJECTIVE
To study the inhibitory effects of benzisoselenothiazolidone sulfonamide derivatives on cyclooxygenase.


METHODS
6-Keto-PGF1 alpha and PGE2 were assayed by radioimmunoassay (RIA) method; mRNA expression of COX-1 and COX-2 were assayed by reverse transcription-polymerase chain reaction (RT-PCR) method.


RESULTS
Compound A [N-4-(4-methoxyphenyl-aminosulfonyl)-benziososelenothiazolidone] and B [N-4-(4-fluorophenyl-aminosulfonyl)-benzoisoselenothiazolidone] were two benzoisoselenothiazolidone sulfonamide derivatives, which can inhibit COX activity with IC50 of 1.5 x 10(-8) mol.L-1 and 5.0 x 10(-8) mol.L-1 for COX-2, as well as IC50 of 1.5 x 10(-5) mol.L-1 and 2.8 x 10(-5) mol.L-1 for COX-1. The ratio of IC50 COX-1/IC50 COX-2 of compound A and B are 1,000 and 560, respectively. They both can inhibit COX-2 mRNA expression in cultured rat peritoneal macrophages stimulated with LPS (1 microgram.mL-1), and have no effect on COX-1 mRNA expressions.


CONCLUSIONS
Compound A and B, two benzoisoselenothiazolidone sulfonamide derivatives, both are selective inhibitory agents of COX-2, and possess inhibitory effects on 5-lipoxygenase and cyclooxygenase.
Guo
Y
Y
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Xiao
Y X
YX
Guo
Z R
ZR
Cheng
G F
GF
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; C481179:N-4-(4-fluorophenylaminosulfonyl)benzoisoselenothiazolidone; C481178:N-4-(4-methoxyphenylaminosulfonyl)benzoisoselenothiazolidone; D016566:Organoselenium Compounds; D012333:RNA, Messenger; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C496513:Ptgs1 protein, rat