Towards safer anti-inflammatory therapy: synthesis of new thymol-pyrazole hybrids as dual COX-2/5-LOX inhibitors.

ABSTRACT: New thymol - 1,5-disubstitutedpyrazole hybrids were synthesised as dual COX-2/5-LOX inhibitors. Compounds 8b, 8g, 8c, and 4a displayed in vitro inhibitory activity against COX-2 (IC₅₀ = 0.043, 0.045, 0.063, and 0.068 µM) nearly equal to celecoxib (IC₅₀ = 0.045 µM) with high SI (316, 268, 204, and 151, respectively) comparable to celecoxib (327). All target compounds, 4a-c and 8a-i, showed in vitro 5-LOX inhibitory activity higher than reference quercetin. Besides, they possessed in vivo inhibition of formalin-induced paw oedema higher than celecoxib. In addition, compounds 4a, 4b, 8b, and 8g showed superior gastrointestinal safety profile (no ulceration) as celecoxib and diclofe

SUBMITTER: El-Miligy MMM 

PROVIDER: S-EPMC9704104 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature