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 so-obtained 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.
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This work was supported by a research grand from the FNRS (FRSM 3.4.625.07 and FRFC 2.4.654.06).
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Aichaoui, H., Guenadil, F., Kapanda, C.N. et al. Synthesis and pharmacological evaluation of antioxidant chalcone derivatives of 2(3H)-benzoxazolones. Med Chem Res 18, 467–476 (2009). https://doi.org/10.1007/s00044-008-9143-y
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DOI: https://doi.org/10.1007/s00044-008-9143-y