Synthesis, In vitro and Docking Studies of New Flavone Ethers as α-Glucosidase Inhibitors

We report herein the synthesis, α-glucosidase inhibition and docking studies for a series of 3-15 new flavones. A simple nucleophilic substitution reaction takes place between 3'hydroxyflavone (2) with halides to afford the new flavones. Chalcone (1), 3'hydroxyflavone (2) and the newly synthesized flavones (3-15) were being evaluated for their ability to inhibit activity of α-glucosidase. Compounds 2, 3, 5, 7-10 and 13 showed good inhibitory activity with IC50 values ranging between 1.26 and 36.44 μM as compared to acarbose (IC50 = 38.25 ± 0.12 μM). Compounds 5 (5.45 ± 0.08 μM), 7 (1.26 ± 0.01 μM) and 8 (8.66 ± 0.08 μM) showed excellent inhibitory activity, and this may be due to trifluoromethyl substitution that is common for these compounds. Compound 7, a 2,5-trifluoromethyl-substituted compound, recorded the highest inhibition activity, and it is thirty times better than the standard drug. Docking studies for compound 7 suggest that both trifluoromethyl substituents are well positioned in a binding pocket surrounded by Phe300, Phe177, Phe157, Ala278, Asp68, Tyr71 and Asp214. The ability of compound 7 to interact with Tyr71 and Phe177 is extremely significant as they are found to be important for substrates recognition by α-glucosidase.