Benzo [d]isothiazol-3-yl-benzamidines: a Class of Protective Agents on Cultures of Human Cartilage and Chondrocytes Stimulated By IL-1 beta

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, PGE2, 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-1β-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.