Synthesis and biological evaluation of novel chromonyl enaminones as -glucosidase inhibitors

Series of novel chromonyl enaminones 1a-e and 2a-e and 3-alkylated chromones 3a-e were synthesized and evaluated in vitro as -glucosidase inhibitors as well as antioxidant and antifungal agents. Antifungal activity was tested on strains of Candida albicans. Compounds 2a and 2d-e showed good inhibition of the -glucosidase enzyme (IC50=5.5, 0.9, and 1.5mM, respectively), their effect being better than that of 1a-e, 3a-e, and acarbose (the standard, IC50=7.73 +/- 0.9mM). The structure-activity relationship suggests that the phenyl group at the C-3 position of the chromone ring system and the 4-chlorophenyl group at the enaminone moiety (derivatives 2) increased the inhibition of -glucosidase. Compounds 2a-e exhibited a slight antioxidant effect, and compounds 3a-e a moderate antifungal activity against C. albicans (IC50 70.5-83.1 mu g/mL). Docking studies revealed that compounds 2 interact with the -glucosidase residues of the binding pocket. Therefore, these chromone derivatives may be considered as potential -glucosidase inhibitors, as well as antifungal agents against some Candida strains of yeast.