Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition.

ABSTRACT: Based on the observed pharmacophoric structural features for the reported dual COX/15-LOX inhibitors and inspired by the abundance of COX/LOX inhibitory activities reported for the 1,2,4-triazine and quinoline scaffolds, we designed and synthesized novel 1,2,4-triazine-quinoline hybrids (8a-n). The synthesized hybrids were evaluated in vitro as dual COXs/15-LOX inhibitors. The new triazine-quinoline hybrids (8a-n) exhibited potent COX-2 inhibitory profiles (IC₅₀ = 0.047-0.32 μM, SI ∼ 20.6-265.9) compared to celecoxib (IC₅₀ = 0.045 μM, SI ∼ 326). Moreover, they revealed potent inhibitory activities against 15-LOX enzyme compared to reference quercetin (IC₅₀ = 1.81-3.60 vs. 3.34 μM). Hybrid 8e was the most potent and selective dual COX-2/15-LOX inhibitor (COX

SUBMITTER: Ghanim AM 

PROVIDER: S-EPMC8165015 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature