title: Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies.
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 compounds 2b and 2c were characterized by single-crystal X-ray diffraction. Compound 1c, 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 Ki value of 2.39 μM. Molecular docking studies were also performed for most active compound 1c and one of least active compound 2c in order to determine the probable binding model into active site of PON1 and validation of the experimental results.
authors.affiliation: Inönü University, Faculty of Arts and Science, Department of Chemistry, 44280 Malatya, Turkey. Electronic address: mert.karatas@inonu.edu.tr.
authors.forename: Mert Olgun
authors.initials: MO
authors.lastname: Karataş
authors.affiliation: Inönü University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 44280 Malatya, Turkey.
authors.forename: Harun
authors.initials: H
authors.lastname: Uslu
authors.affiliation: Inönü University, Faculty of Arts and Science, Department of Chemistry, 44280 Malatya, Turkey.
authors.forename: Bülent
authors.initials: B
authors.lastname: Alıcı
authors.affiliation: Süleyman Demirel University, Faculty of Pharmacy, Department of Biochemistry, 32260 Isparta, Turkey.
authors.forename: Başak
authors.initials: B
authors.lastname: Gökçe
authors.affiliation: Balıkesir University, Faculty of Arts and Science, Department of Chemistry, 10145 Balıkesir, Turkey. Electronic address: ngencer@balikesir.edu.tr.
authors.forename: Nahit
authors.initials: N
authors.lastname: Gencer
authors.affiliation: Balıkesir University, Faculty of Arts and Science, Department of Chemistry, 10145 Balıkesir, Turkey.
authors.forename: Oktay
authors.initials: O
authors.lastname: Arslan
authors.affiliation: Giresun University, Faculty of Education, Department of Computer Education and Instructional Technology, 28100 Giresun, Turkey.
authors.forename: N Burcu
authors.initials: NB
authors.lastname: Arslan
authors.affiliation: Ondokuz Mayıs University, Faculty of Arts and Sciences, Department of Physics, 55139 Samsun, Turkey.
authors.forename: Namık
authors.initials: N
authors.lastname: Özdemir
mesh_terms: D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D007093:Imidazoles; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Benzimidazolium; Coumarin; Imidazolium; Inhibition; Molecular docking; Paraoxonase 1