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

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 o...

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Bibliographic Details
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
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Summary: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.
ISSN:1860-7187