Synthesis and biological evaluation of novel chromonyl enaminones as α-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 α-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 α-glucosidase enzyme (IC 50 = 5.5, 0.9, and 1.5 mM, respectively), their effect being better than that of 1a – e , 3a – e , and acarbose (the standard, IC 50 = 7.73 ± 0.9 mM). 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 α-glucosidase. Compounds 2a – e exhibited a slight antioxidant effect, and compounds 3a – e a moderate antifungal activity against C. albicans (IC 50 70.5–83.1 µg/mL). Docking studies revealed that compounds 2 interact with the α-glucosidase residues of the binding pocket. Therefore, these chromone derivatives may be considered as potential α-glucosidase inhibitors, as well as antifungal agents against some Candida strains of yeast.