Benzo[d]isothiazol-3-yl-benzamidines: a class of protective agents on culture of human cartilage and chondrocytes stimulated by IL-1beta

• Published in: ChemMedChem 2007-01, Vol.2 (1), p.113-119
• Main Authors: Vicini, Paola, Incerti, Matteo, Cardile, Venera, Garufi, Floriana, Ronsisvalle, Simone, Panico, Anna Maria
• Format: Article
• Language: English
• Subjects: Amidines - chemistry; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Benzamidines - chemical synthesis; Benzamidines - pharmacology; Cartilage - drug effects; Cartilage - metabolism; Cells, Cultured; Chondrocytes - drug effects; Chondrocytes - metabolism; Cyclooxygenase 2 - metabolism; Glycosaminoglycans - metabolism; Humans; Interleukin-1beta - pharmacology; Matrix Metalloproteinase 3 - metabolism; Nitric Oxide - metabolism; Osteoarthritis - drug therapy; Protective Agents - chemical synthesis; Protective Agents - pharmacology; Protective Agents - therapeutic use; Reactive Oxygen Species - metabolism; Structure-Activity Relationship
• ISSN: 1860-7187

New derivatives of N-benzo[d]isothiazol-3-yl-benzamidine 6 a were synthesized as nonacidic anti-inflammatory/antidegenerative agents. We investigated the influence of the amidines 6 a-j on the production of NO, PGE(2), MMP-3, COX-2, ROS, and GAGs, key molecules involved in cartilage destruction in osteoarthritic diseases. The antidegenerative properties of the novel designed derivatives 6 b-j were improved with respect to N-benzo[d]isothiazol-3-yl-benzamidine 6 a. All of the compounds 6 a-j promoted the reduction of most of the IL-1beta-induced harmful effects. Derivatives 6 d, 6 h, and 6 j were the most potent of all the tested compounds, particularly in the human chondrocyte culture model.