A set of 17 coumarin and 2 chromone derivatives with known inhibitory activity toward monoamine oxidase (MAO) A and B were tested as acetylcholinesterase (AChE) inhibitors. All compounds inhibited AChE with values in the micromolar range (3-100 microM). A kinetic study showed that most compounds acted as noncompetitive AChE inhibitors. This finding may be of interest in the context of Alzheimer's disease because recent observations suggest that MAO and AChE inhibition might decrease beta-amyloid deposition.

Acetylcholinesterase (AChE) inhibitors are currently the only approved therapy for the treatment of Alzheimer's disease, only a limited number of drugs are commercially available. A library of non-alkaloidal natural compounds was investigated. To this end, a convenient microtitre plate method for assaying AChE inhibition, which allows a complete kinetic analysis of AChE inhibitors, was developed. Seven active compounds with Ki values in the micromolar range were identified, six of which were xanthones. This is the first report that a promising potential for AChE inhibition exists in such non-nitrogenous natural compounds. Furthermore, four xanthones among these xanthones had already been described as monoamine oxidase (MAO) inhibitors, making then dual AChE/MAO inhibitors of great interest.

In this work, a convenient test of antioxidant activity was developed, with BChE-contaminated HSA as the target of AAPH-induced oxidation and its esterase activity as the marker of protein integrity or degradation. The method is relatively simple, of low cost, and convenient to use. Its application to natural polyphenols showed that quercetin (1), verbascoside (2), chlorogenic acid (3), caffeic acid (4), 1,3,6,7-tetrahydroxyxanthone (5), and mangiferin (6), are good antioxidants (IC 50 < 9 mm). 1,5-Dihydroxy-3-methoxyxanthone (7), flemichin D (8), and cordigone (9) showed modest activities (ca. 50 mm < IC 50 < 350 mm), whereas danthrone (10) was inactive. Complementary experiments with two of the more active antioxidants, namely quercetin (1) and chlorogenic acid (3) showed that both antioxidants were better radical scavengers than chain-breaking antioxidants. The relative adiabatic oxidation potential (DH ox ), the relative H-bond dissociation energy (DH abs ), and the first oxidation potential measured by cyclic voltammetry were found to be related to the radical-scavenging activity of these antioxidants.