Synthesis, ?-glucosidase inhibition and molecular docking studies of natural product 2-(2-phenyethyl) chromone analogues

A series of natural product (2-phenyethyl)chromone analogues (3-34) were designed, synthesized, and screened for their a-glucosidase inhibitory activity. The results indicated that some of the synthesized derivatives displayed inhibitory activities against a-glucosidase with IC50 values ranging from 11.72 +/- 0.08 to 85.58 +/- 2.30 lM when compared to the standard drug acarbose (IC50 = 832.22 +/- 2.00 lM). Among them, compound 4 with a hydroxyl group at the 7-position of chromone and a chloro group at the 4-position of the benzene ring, displayed the most significant inhibitory activity with the IC50 value of 11.72 +/- 0.08 lM. The inhibitory mechanism of compound 4 against a-glucosidase was studied by enzyme kinetic, circular dichroism spectra, fluorescence quenching, and molecular docking. Sucrose loading test in vivo further demonstrated that it could decrease blood glucose levels after sucrose administration in normal Kunming mice. In vitro cytotoxicity showed that 4 exhibited low cytotoxicity against normal human cell lines. The ADME study suggested that all compounds are likely to be orally active as they obeyed Lipinski's rule of five. In summary, our studies showed that these derivatives are a new class of a-glucosidase inhibitors. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study designed, synthesized, and screened a series of natural product (2-phenyethyl)chromone analogues for their a-glucosidase inhibitory activity. The results showed that some of the synthesized derivatives exhibited inhibitory activities against a-glucosidase, with compound 4 displaying the most significant inhibitory activity. The compound showed potential for treating diabetes with low cytotoxicity against normal cells. It represents a new class of a-glucosidase inhibitors.