Some coumarins and benzoxazinones as potent paraoxonase 1 inhibitors
Küçük Resim Yok
Tarih
2016
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Taylor & Francis Ltd
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
In this study, we aimed to investigate the effect of some coumarin and benzoxazinone derivatives on the activity of human PON1. Human serum paraoxonase 1 was purified from fresh human serum blood by two-step procedures that are ammonium sulfate precipitation (60-80%) and then hydrophobic interaction chromatography (Sepharose 4B, L-tyrosine and 1-napthylamine). The enzyme was purified 232-fold with a final specific activity of 27.1 U/mg. In vitro effects of some previously synthesized ionic coumarin or benzoxazinone derivatives (1-21) on purified PON1 activity were investigated. Compound 14 (1-(2,3,4,5,6)-pentamethyl-benzyl-3-(6,8-dimethyl-2H-chromen-2-one-4-yl)) benzimidazolium chloride was found out as the strongest inhibitor (IC50 = 7.84 mu M) for PON1 among the compounds. Kinetic investigation and molecular docking study were evaluated for one of the most active compounds (compound 12) and obtained data showed that this compound is competitive inhibitor of PON1 and interact with Leu262 and Ser263 in the active site of PON1. Moreover, coumarin derivatives were found out as the more potent inhibitors for PON1 than benzoxazinone derivatives.
Açıklama
Anahtar Kelimeler
Benzoxazinone, coumarin, docking, inhibition, paraoxonase
Kaynak
Journal of Enzyme Inhibition and Medicinal Chemistry
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
31
Sayı
6
