Benzoflavones as cholesterol esterase inhibitors: Synthesis, biological evaluation and docking studies. Issue 4 (15th February 2017)

• Record Type: Journal Article
• Authors: Singh, Harbinder; Singh, Jatinder Vir; Gupta, Manish K.; Singh, Palwinder; Sharma, Sahil; Nepali, Kunal; Bedi, Preet Mohinder S.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 4(2017)
• Page Start: 850
• Page End: 854
• Publication Date: 2017-02-15
• Subjects: Benzoflavone -- Baker Venkataraman rearrangement -- Cholesterol esterase inhibition -- Enzyme kinetics -- Docking studies; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.01.020
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A library of forty 7, 8-benzoflavone derivatives was synthesized and evaluated for their inhibitory potential against cholesterol esterase (CEase). Among all the synthesized compounds seven benzoflavone derivatives (A -7, A -8, A -10, A -11, A -12, A -13, A -15 ) exhibited significant inhibition against CEase in in vitro enzymatic assay. CompoundA -12 showed the most promising activity with IC50 value of 0.78 nM against cholesterol esterase. Enzyme kinetic studies carried out forA -12, revealed its mixed-type inhibition approach. Molecular protein–ligand docking studies were also performed to figure out the key binding interactions ofA -12 with the amino acid residues of the enzyme's active site. TheA -12 fits well at the catalytic site and is stabilized by hydrophobic interactions. It completely blocks the catalytic assembly of CEase and prevents it to participate in ester hydrolysis mechanism. The favorable binding conformation ofA -12 suggests its prevailing role as CEase inhibitor.