In Vitro Inhibition Effect of Some Dihydroxy Coumarin Compounds on Purified Human Serum Paraoxonase 1 (PON1).

Erzengin, Mahmut; Basaran, Ismet; Cakir, Umit; Aybey, Aynur; Sinan, Selma

Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro inhibition effect of some dihydroxy coumarin compounds namely 6,7-dihydroxy-3-(2-methylphenyl)-2H-chromen-2-one (A), 6,7-dihydroxy-3-(3-methylphenyl)-2H-chromen-2-one (B) and 6,7-dihydroxy-3-(4-methylphenyl)-2H-chromen-2-one (C) on purified PON1 were investigated by using paraoxon as a substrate. PON1 was purified using two-step procedures, namely ammonium sulphate precipitation and Sepharose-4B- l-tyrosine-1-naphthylamine hydrophobic interaction chromatography. The purified enzyme had a specific activity of 11.76 U/mg. The dihydroxy coumarin derivatives of A and B compounds inhibited PON1 enzyme activity in a noncompetitive inhibition manner with K of 0.0080 ± 0.256 and 0.0003 ± 0.018 mM values, respectively. C compound exerted an uncompetitive inhibition of PON1 enzyme activity with K of 0.0010 ± 0.173 mM. Moreover, dihydroxy coumarin derivatives of A, B and C compounds were effective inhibitors on purified human serum PON1 activity with IC of 0.012, 0.022 and 0.003 mM values, respectively. IC value of unsubstituted 6,7 dihydroxy coumarin was found as 0.178 mM. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

ESTRADIOL; FERTILIZATION in vitro; SERUM; PARAOXONASE; LACTONES

Applied Biochemistry & Biotechnology, 2012, Vol 168, Issue 6, p1540

0273-2289

Academic Journal

10.1007/s12010-012-9876-4