Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies. Issue 6 (15th March 2016)

• Record Type: Journal Article
• Authors: Karataş, Mert Olgun; Uslu, Harun; Alıcı, Bülent; Gökçe, Başak; Gencer, Nahit; Arslan, Oktay; Arslan, N. Burcu; Özdemir, Namık
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 6(2016)
• Page Start: 1392
• Page End: 1401
• Publication Date: 2016-03-15
• Subjects: Benzimidazolium -- Coumarin -- Imidazolium -- Inhibition -- Molecular docking -- Paraoxonase 1; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.02.012
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Paraoxonase (PON) is a key enzyme in metabolism of living organisms and decreased activity of PON1 was acknowledged as a risk for atherosclerosis and organophosphate toxicity. The present study describes the synthesis, characterization, PON1 inhibitory properties and molecular docking studies of functionalized imidazolium and benzimidazolium salts (1a –5g ). The structures of all compounds were elucidated by IR, NMR, elemental analysis and structures of compounds2b and2c were characterized by single-crystal X-ray diffraction. Compound1c, a coumarin substituted imidazolium salt showed the best inhibitory effect on the activity of PON1 with good IC50 value (6.37 μM). Kinetic investigation was evaluated for this compound and results showed that this compound is competitive inhibitor of PON1 with K i value of 2.39 μM. Molecular docking studies were also performed for most active compound1c and one of least active compound2c in order to determine the probable binding model into active site of PON1 and validation of the experimental results.