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

作者：Alim Zuhal^*; Kilic Deryanur; Koksal Zeynep; Beydemir Sukru; Ozdemir Hasan

来源：Journal of Biochemical and Molecular Toxicology, 2017, 31(10): e21950.

DOI：10.1002/jbt.21950

• atherosclerosis
• inhibition
• molecular docking
• paraoxonase-1
• sulfonamide

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-sulfamoilaniline, 4-amino-3-methylbenzenesulfanilamide, sulfisoxazole, sulfisomidine, and 5-amino-2-methylbenzenesulfonamide). IC50, K-i values, and inhibition types were calculated for each sulfonamide. 2-amino-5-methyl-1,3-benzenedisulfonamide and 2-chloro-4-sulfamoilaniline 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.

• 出版日期2017-10