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.