The validity of the chalcone scaffold for the design of inhibitors of monoamine oxidase has previously been illustrated. In a systematic attempt to investigate the effect of heterocyclic substitution on the monoamine oxidase inhibitory properties of this versatile scaffold, a series of furanochalcones were synthesized. The results demonstrate that these furan substituted phenylpropenones exhibited moderate to good inhibitory activities towards MAO-B, but showed weak or no inhibition of the MAO-A enzyme. The most active compound, 2E-3-(5-chlorofuran-2-yl)-1-(3-chlorophenyl)prop-2-en-1-one, exhibited an IC50 value of 0.174 μM for the inhibition of MAO-B and 28.6 μM for the inhibition of MAO-A. Interestingly, contrary to data previously reported for chalcones, these furan substituted derivatives acted as reversible inhibitors, while kinetic analysis revealed a competitive mode of binding.
Keywords: Chalcone; Competitive; MAO-B; Monoamine oxidase; Reversible inhibition.
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