Affiliations 

  • 1 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, Selangor, DE, 42300, Malaysia
  • 2 Institute of Advance Research Studies in Chemical Sciences, University of Sindh, 76080, Jamshoro, Pakistan
  • 3 Department of Chemistry, Hazara University, 21300, Mansehra, Pakistan
  • 4 Pharmaceutical Design and Simulation Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Pulau Pinang, Malaysia
  • 5 H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
Chem Biol Drug Des, 2016 Mar;87(3):361-73.
PMID: 26362113 DOI: 10.1111/cbdd.12666

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.