Synthesis,In vitro and Docking Studies of New Flavone Ethers as α‐Glucosidase Inhibitors |
| |
Authors: | Syahrul Imran Muhammad Taha Nor Hadiani Ismail Syed Muhammad Kashif Fazal Rahim Waqas Jamil Habibah Wahab Khalid Mohammed Khan |
| |
Affiliation: | 1. Atta‐ur‐Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Selangor, DE, Malaysia;2. Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, Selangor, DE, Malaysia;3. Institute of Advance Research Studies in Chemical Sciences, University of Sindh, Jamshoro, Pakistan;4. Department of Chemistry, Hazara University, Mansehra, Pakistan;5. Pharmaceutical Design and Simulation Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia;6. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan |
| |
Abstract: | 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 μ m as compared to acarbose (IC50 = 38.25 ± 0.12 μ m ). Compounds 5 (5.45 ± 0.08 μ m ), 7 (1.26 ± 0.01 μ m ) and 8 (8.66 ± 0.08 μ m ) 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. |
| |
Keywords: | docking enzyme inhibition ether linkage flavone α ‐glucosidase |
|
|