title: Effect of a novel anti-inflammatory drug, 2-(10, 11-dihydro-10-oxo-dibenzo[b,f]-thiepin-2-yl)propionic acid (CN-100), on the proteoglycan biosynthesis in articular chondrocytes and prostaglandin E2 production in synovial fibroblasts.
abstract: The effect of a novel nonsteroidal anti-inflammatory drug, 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl)propionic acid (CN-100), on the biosynthesis of proteoglycans in chondrocytes of rat femoral head articular cartilage was studied. Sodium salicylate and hydrocortisone inhibited significantly the biosynthesis proteoglycans, but CN-100 did not affect the biosynthesis of glycosaminoglycan chains nor their sulfation. The effect of CN-100 on the interleukin 1-induced biosynthesis of prostaglandin E2 (PGE2) and tissue collagenase in rabbit and human rheumatoid synovial fibroblasts was also examined. CN-100 did not inhibited directly the collagenase production, but significantly prevent the biosynthesis of PGE2 known as an inflammatory mediator. The 50% inhibitory concentration (IC50) of CN-100 on PGE2 of rabbit and human fibroblasts were 3.8 x 10(-9) M and 2.4 x 10(-8) M, respectively; an inhibitory effect of CN-100 was equivalent to that of a control drug, hydrocortisone (2.0 x 10(-9) M and 1.7 x 10(-8) M, respectively). These results indicate that CN-100 is a potent anti-inflammatory drug without affecting the proteoglycan biosynthesis.
authors.affiliation: Department of Biochemistry, Tokyo College of Pharmacy, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001582:Benzothiepins / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D003012:Microbial Collagenase / Q000096:biosynthesis; D011509:Proteoglycans / Q000096:biosynthesis*; D011817:Rabbits; D051381:Rats; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001582:Benzothiepins; D007375:Interleukin-1; D011509:Proteoglycans; C051758:CN 100; D003012:Microbial Collagenase; D015232:Dinoprostone; D006854:Hydrocortisone; D007213:Indomethacin