2-Styrylchromones Modulate Prostaglandins Production through the Inhibition of COX-2 ^†

Abstract

2-Styrylchromones (2-SC) are heterocyclic compounds with a structure of at least 17 carbons and a styryl group attached to a benzoannelated γ-pyrone ring. Although the anti-inflammatory potential of 2-SC has become a subject of interest, their effects in inflammatory pathways are still unexplored. Therefore, to better understand the mechanisms of anti-inflammatory action of 2-SC, this study investigated the influence of 10 hydroxylated and methoxylated 2-SC on the inhibitory activity of cyclooxygenase (COX-2), through an in vitro non-cellular assay and an ex vivo assay in human whole blood, which were based on the fluorometric detection of prostaglandin (PG) G₂ and colorimetric detection of PGE₂, respectively. A 2-SC hydroxylated at C-7 and C-8 on the A-ring and C-3′ and C-4′ on the B-ring was the most active in the direct inhibition of COX-2 activity, whereas a 2-SC methoxylated at C-4′ on the B-ring was the most active in the ex vivo inhibition of PGE₂ production. The obtained results suggest that the presence of OH groups, especially at C-8 on the A-ring, favor the direct inhibition of COX-2. Conversely, for inhibition of PGE₂ production in a more complex matrix, human blood, it is the presence of an OCH₃ at C-4′ on the B-ring that seems to be important.