Evaluation of the in vivo and in vitro anti-inflammatory activity of a new hybrid NSAID tetrahydropyran derivative

Evaluate the anti-inflammatory activity in vivo and in vitro of cis-(+/-)-acetate of 4-chloro-6-(naphtalene-1-yl)-tetrahydro2H-pyran-2-yl) methyl 2-(2-(2,6-diclorofenylamine) phenyl (LS19). Male Swiss mice were analyzed in the paw edema, ear edema, and air pouch tests, and in vitro COX inhibition, cytotoxicity evaluation, and cytokine and nitric oxide determination tests. The compound showed effect on the carrageenan- and bradykinin-induced paw edema and capsaicin-induced ear edema tests. In addition, the compound was able to inhibit leukocyte migration to decrease the levels of the pro-inflammatory cytokines tumor necrosis factor a (TNF-a) and interleukin 113 (IL-113) and to increase the levels of the anti-inflammatory cytokine IL-10. The compound was also able to reduce levels of TNF-a, IL-6, and nitric oxide in the RAW 264.7 cell line and to inhibit COX activity. LS19 did not induce any significant changes in the viability of RAW 264.7 cells, demonstrating safety for these cell lines. The compound LS19 did not reduce the production of gastric mucus and induced a smaller increase in the extent of gastric lesions than that developed by the administration of diclofenac. In summary, the new compound proved to be safer and it had additional mechanisms compared to diclofenac.