1,4-Diaryl-1,2,3-triazole neolignan-celecoxib hybrids inhibit experimental arthritis induced by zymosan.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage damage. Anti-inflammatories are widely used in the management of RA, but they can have side effects such as gastrointestinal and/or cardiovascular disorders. Studies published by our group showed that the synthesis of hybrid triazole analogs neolignan-celecoxib containing the substituent groups sulfonamide (L15) or carboxylic acid (L18) exhibited anti-inflammatory activity in an acute model of inflammation, inhibited expression of P-selectin related to platelet activation and did not induce gastric ulcer, minimizing the related side effects. Incontinuation, thepresentstudyevaluated the anti-inflammatory effects of these analogs in an experimental model of arthritisand on the functions of one of the important cells in this process, macrophages. Mechanical hyperalgesia, joint edema, leukocyte recruitment to the joint and damage to cartilage in experimental arthritis and cytotoxicity, spread of disease, phagocytic activity and nitric oxide (NO) and hydrogen peroxide production by macrophages were evaluated. Pre-treatment withL15andL18 reduced mechanical hyperalgesia, joint edema and the influx of leukocytes into the joint cavity after different periods of the stimulus. The histological evaluation of the joint showed that L15andL18reduced cartilage damage and there was no formation of rheumatoidpannus. Furthermore,L15andL18 were non-cytotoxic. The analogs inhibited the spreading, the production of NO and hydrogen peroxide.L15 decreased the phagocytosis. Therefore, L15andL18may be potential therapeutic prototypes to treat chronic inflammatory diseases such as RA.