title: Synthesis, In vitro and Docking Studies of New Flavone Ethers as α-Glucosidase Inhibitors.
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 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.
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, Selangor, DE, 42300, Malaysia.|Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, Selangor, DE, 40450, Malaysia.
authors.forename: Syahrul
authors.initials: S
authors.lastname: Imran
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, Selangor, DE, 42300, Malaysia.|Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, Selangor, DE, 40450, Malaysia.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Taha
authors.affiliation: Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, Selangor, DE, 42300, Malaysia.|Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, Selangor, DE, 40450, Malaysia.
authors.forename: Nor Hadiani
authors.initials: NH
authors.lastname: Ismail
authors.affiliation: Institute of Advance Research Studies in Chemical Sciences, University of Sindh, 76080, Jamshoro, Pakistan.
authors.forename: Syed Muhammad
authors.initials: SM
authors.lastname: Kashif
authors.affiliation: Department of Chemistry, Hazara University, 21300, Mansehra, Pakistan.
authors.forename: Fazal
authors.initials: F
authors.lastname: Rahim
authors.affiliation: Institute of Advance Research Studies in Chemical Sciences, University of Sindh, 76080, Jamshoro, Pakistan.
authors.forename: Waqas
authors.initials: W
authors.lastname: Jamil
authors.affiliation: Pharmaceutical Design and Simulation Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Pulau Pinang, Malaysia.
authors.forename: Habibah
authors.initials: H
authors.lastname: Wahab
authors.affiliation: H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry; D047309:Flavones / Q000737:chemistry*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D021241:Spectrometry, Mass, Electrospray Ionization; D000520:alpha-Glucosidases / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D004987:Ethers; D047309:Flavones; D000520:alpha-Glucosidases
keywords: docking; enzyme inhibition; ether linkage; flavone; α-glucosidase