Med Chem Res (2009) 18:467–476

Synthesis and pharmacological evaluation of antioxidant chalcone derivatives
of 2(3H)-benzoxazolones

Hocine Aichaoui Æ Faouzi Guenadil Æ Coco N. Kapanda Æ Didier M. Lambert Æ
Christopher R. McCurdy Æ Jacques H. Poupaert

Received: 21 April 2008 / Accepted: 28 October 2008 / Published online: 4 December 2008

Birkha¨user Boston 2008

Abstract Chalcones featuring an analgesic/anti-inflammatory pharmacophore,
i.e., the 2(3H)-benzoxazolone heterocycle, on the one hand, and a radical scavenger
moiety, i.e., 2,6-di-t-butylphenol, on the other hand were synthesized by condensation
of a ketone 2(3H)-benzoxazolone precursor with 3,5-di-t-butyl-4-
hydroxybenzaldehyde. Among the various methods explored (acid homogenous or
heterogenous catalysis, base catalysis), heterogenous catalysis conditions using KSF
Montmorillonite were found to be the most convenient. The E-geometry of the soobtained
chalcones was ascertained both by 1H and 13C-nuclear magnetic resonance
(NMR) spectroscopy as well as B3LYP/6-31G** quantum mechanics calculations.
Chalcones 1–8 were pharmacologically evaluated in vitro for their ability to prevent
human low-density lipoprotein (LDL) copper-induced oxidation using Cu2? as
oxidizing agent. Compound 4 emerged as the most promising agent as it was able to
inhibit copper-mediated human LDL oxidation with an activity ten times greater
than that of Probucol, a reference antioxidant drug.