Assessment of the inhibitory effects and molecular docking of some sulfonamides on human serum paraoxonase 1

Abstract

Paraoxonase-1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. Due to the PON1's crucial functions, inhibitors and activators of PON1 must be known for pharmacological applications. In this study, we investigated the in vitro effects of some sulfonamides compounds on human serum PON1 (hPON1). For this aim, we purified the hPON1 from human serum with high specific activity by using simple chromatographic methods, and after the purification processes, we investigated in vitro interactions between the enzyme and some sulfonamides (2-amino-5-methyl-1,3-benzenedisulfonamide, 2-chloro-4-sülfamoilaniline, 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, sulfisomidine, and 5-amino-2-methylbenzenesulfonamide). IC , K values, and inhibition types were calculated for each sulfonamide. 2-amino-5-methyl-1,3-benzenedisulfonamide and 2-chloro-4-sülfamoilaniline exhibited noncompetitive inhibition effect, whereas 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, and sulfisomidine exhibited mixed type inhibition. On the other hand, 5-amino-2-methylbenzenesulfonamide showed competitive inhibition and so molecular docking studies were performed for this compound in order to assess the probable binding mechanism into the active site of hPON1.

Synthesis and characterization of four novel palladium(II) and platinum(II) complexes with 1‐(2‐aminoethyl)pyrrolidine, diclofenac and mefenamic acid: In vitro effect of these complexes on human serum paraoxanase1 activity

“…K i values (0.057–0.212 mM) obtained in present study were more effective than K i values (0.116–0.434 mM) in our previous studies . Furthermore, Alim and Beydemir investigated in vitro interactions between the PON1 enzyme and some sulfonamides. In this study, these sulfonamides have inhibition constants in the range of 0.151–1.156 mM for human serum PON1.…”

“…Complex 3 and 4 showed less inhibition activity than 1 and 2 complexes, with K i of 0.155 and 0.212 mM, respectively. Complex 1–4 showed more inhibitory effect compared with recently reported PON1 inhibitors in the literature . Effects of different copper(II) complexes, which are derived dicarboxylic acid and naproxen, for PON1 enzyme have been researched until now by our group.…”

A potential risk factor for paraoxonase 1: in silico and in-vitro analysis of the biological activity of proton-pump inhibitors

“…In this study was applied the same procedure with our previous studies and PON1 was purified from human serum in three simple chromatographic steps. These results confirm the findings of a great deal of the previous works . After, the pantoprazole, omeprazole and esomeprazole as PPIs were tested on paraoxonase activity of the PON1 enzyme.…”

In Vitro and In Silico Studies on the Toxic Effects of Antibacterial Drugs as Human Serum Paraoxonase 1 Inhibitor

“…In this study, it was applied the identical procedure used by our group in previous studies, and PON1 purified from human serum in three simple steps . The purification resulted in with a yield of 20.25%, a specific activity of 3880.83 EU/mg proteins, and the enzyme was purified approximately 240‐fold.…”