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Synthesis, In vitro and Docking Studies of New Flavone Ethers as α ‐Glucosidase Inhibitors
Author(s) -
Imran Syahrul,
Taha Muhammad,
Ismail Nor Hadiani,
Kashif Syed Muhammad,
Rahim Fazal,
Jamil Waqas,
Wahab Habibah,
Khan Khalid Mohammed
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12666
Subject(s) - flavones , trifluoromethyl , chemistry , chalcone , docking (animal) , acarbose , stereochemistry , ic50 , nucleophilic substitution , semicarbazone , in vitro , enzyme , medicinal chemistry , biochemistry , organic chemistry , chromatography , medicine , alkyl , nursing
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 IC 50 values ranging between 1.26 and 36.44 μ m as compared to acarbose ( IC 50 = 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.