Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies

KARATAŞ M. O., USLU H., ALICI B., GÖKÇE B., Gencer N., Arslan O., ...Daha Fazla

BIOORGANIC & MEDICINAL CHEMISTRY, cilt.24, sa.6, ss.1392-1401, 2016 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 24 Sayı: 6
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1016/j.bmc.2016.02.012
  • Dergi Adı: BIOORGANIC & MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1392-1401
  • Anahtar Kelimeler: Benzimidazolium, Coumarin, Imidazolium, Inhibition, Molecular docking, Paraoxonase 1, IN-VITRO, SERUM, PURIFICATION, ANTIBIOTICS, DERIVATIVES, MECHANISM, PON1
  • İnönü Üniversitesi Adresli: Evet

Özet

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 mu M). Kinetic investigation was evaluated for this compound and results showed that this compound is competitive inhibitor of PON1 with K-1, value of 2.39 mu M. 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. (C) 2016 Elsevier Ltd. All rights reserved.