Synthesis of 1,2-naphthoquinone derivatives as α-glucosidase inhibitors

Abstract

For a couple of decades the bioactivity of quinone has been considered as privileged structure-based drug design. In this research, 4-phenylamino, 4-alkylamino, 4-alkylphenylamino, 4-phenoxy and other derivatives of 1,2-naphthoquinone were synthesized, evaluated for their anti α-glucosidase activity and elucidated for their structure-activity relationship. The results indicated that multiple factors affecting to the α-glucosidase inhibition included π-π interaction, hydrophobic interaction and hydrogen bonding with the enzyme. In general, the main factor affecting the activity was the more favorable 1,2-dione production. The presence of electron withdrawing substituents on the phenyl ring and heteroatom linker bound to the quinone skeleton increased the activity. The most active compounds were 4-(4-nitrophenylamino)-1,2-naphthoquinone (29) and 4-methoxy-1,2-naphthoquinone (64) with IC50 value of 14.59 µM and 11.39 µM, respectively, which were better than current anti-diabetes drug, acarbose (IC50 = 93.63 µM).