Quercitylcinnamates, a new series of antidiabetic bioconjugates possessing α-glucosidase inhibition and antioxidant

• Novel fifteen quercitylcinnamates (1a–8a) were synthesized.
• Quercityl caffeate (6a) was glucosidase inhibitor more potent than its parent 6.
• 6a retained both glucosidase inhibition and antioxidation.
• Mechanism underlying the inhibition of 6a was mixed-type inhibition.

Antidiabetic agents possessing dual functions, α-glucosidase inhibition and antioxidant, have been accepted to be more useful than currently used antidiabetic drugs because they not only suppress hyperglycemia but also prevent risk of complications. Herein, we design antidiabetic bioconjugates comprising of (+)-proto-quercitol as a glucomimic and cinnamic analogs as antioxidant moieties. Fifteen quercitylcinnamates were synthesized by direct coupling through ester bond in the presence of DCC and DMAP. Particular quercityl esters 6a, 7a and 8a selectively inhibited rat intestinal maltase and sucrose 4–6 times more potently than their parents 6, 7 and 8. Of synthesized bioconjugates, 6a was the most potent inhibitor against maltase and sucrose with IC50 values of 5.31 and 43.65 μM, respectively. Of interest, its inhibitory potency toward maltase was 6 times greater than its parent, caffeic acid (6), while its radical scavenging (SC50 0.11 mM) was comparable to that of commercial antioxidant BHA. Subsequent investigation on mechanism underlying inhibitory effect of 6a indicated that it blocked maltase and sucrose functions by mixed inhibition through competitive and noncompetitive manners.

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