In vitro and in silico evaluations of diarylpentanoid series as α-glucosidase inhibitor

A series of thirty-four diarylpentanoids derivatives were synthesized and evaluated for their alpha-glucosidase inhibitory activity. Eleven compounds (19, 20, 21, 24, 27, 28, 29, 31, 32, 33 and 34) were found to significantly inhibit alpha-glucosidase in which compounds 28, 31 and 32 demonstrated the highest activity with IC50 values ranging from 14.1 to 15.1 mu M. Structure-activity comparison shows that multiple hydroxy groups are essential for alpha-glucosidase inhibitory activity. Meanwhile, 3,4-dihydroxyphenyl and furanyl moieties were found to be crucial in improving alpha-glucosidase inhibition. Molecular docking analyses further confirmed the critical role of both 3,4-dihydroxyphenyl and furanyl moieties as they bound to alpha-glucosidase active site in different mode. Overall result suggests that diarylpentanoids with both five membered heterocyclic ring and polyhydroxyphenyl moiety could be a new lead design in the search of novel alpha-glucosidase inhibitor. (C) 2017 Elsevier Ltd. All rights reserved.