Abstract:
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)-pentamethylbenzyl-3-(6,8-dimethyl-2H-chromen-2-one-4-yl))benzimidazolium
chloride was found out as the
strongest inhibitor (IC50 ¼ 7.84 mM) 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
