Synthesis of new methoxy derivatives of trans 2,3-diaryl-2,3-dihydrobenzofurans and evaluation of their anti-inflammatory activity

Abstract

In the present study we synthesized new methoxy derivatives of trans 2,3-diaryl-2,3-dihydrobenzofurans, starting from suitable trans 2,3-diaryloxiranes, using regio- and stereoselective nucleophilic oxiranyl ring-opening reactions. The compounds were tested as anti-inflammatories in U937 cells. All compounds showed a significant role in inhibiting the NF-κB pathway and were able to restore normal ROS and NO level upon LPS activation. Moreover, regarding inhibition of ACLY, enantioenriched (50% ee) 7a₅₀ showed more potency than the racemic counterpart 7arac, together with a higher reduction of prostaglandin E₂ production, thus suggesting a stereoselective interaction in this pathway.

Keywords: 2,3-diaryl-2,3-dihydrobenzofurans; ACLY activity; Anti-inflammatory activity; NF-κB; ROS and NO levels.