Effects of mono and dinuclear copper(II) complexes derived from non-steroidal anti-inflammatory drug naproxen on human serum paraoxanase1 (PON1) activity

The inhibition of human paraoxonase 1 (PON1, EC 3.1.8.1) enzyme, with two Cu(II) complexes derived from naproxen was investigated by using the paraoxonase activity method with diethyl 4-nitrophenyl phosphate as substrate. The complexes [Cu₂(µ-nap)₄(3-pic)₂] (1) and [Cu(nap)₂(H₂O)(4-pic)₂] (2) decreased the in vitro PON1 activity with different inhibition mechanisms. The inhibition mechanism of complex 1 was uncompetitive whereas complex 2 was noncompetitive inhibitors. In this study, complexes mentioned above showed effective inhibitory activity on PON1.  IC₅₀ values for [Cu₂(µ-nap)₄(3-pic)₂] (1) and [Cu(nap)₂(H₂O)(4-pic)₂] (2) were of 0.109 mM and 0.103 mM for PON1, respectively. K_i values for complex 1 and complex 2 were of 0.116 mM and 0.121 mM for PON1, respectively.

paraoxonase1; inhibition; copper(II) complexes; enzyme; inhibitor

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