The inhibition effects of some sulfonamides on human serum paraoxonase-1 (hPON1)

Abstract

Background: Paraoxonase 1 (PON1) is an antiatherogenic and organophosphate hydrolyzer enzyme. It has important roles including protecting low density lipoprotein (LDL) against oxidation and the detoxification of highly toxic substances. Reducing the levels of this enzyme in patients with diabetes mellitus, cardiovascular diseases, hyperthyroidism, and chronic renal failure is a major risk. Methods: Here, we report on the purification of the human serum PON1 using simple methods and determine the interactions between some sulfonamides and the enzyme. Results: We found that some sulfonamides exhibit potential inhibitor properties for the human serum PON1 with IC50 values in the range of 24.10-201.45 mu M and K-i values in the range of 4.41 +/- 0.52-150.23 +/- 20.73 mu M. The sulfonamides showed different inhibition mechanisms. We determined that sulfonamides 1, 2, 4, 5, 8, and 9 showed a non-competitive inhibition effect whereas sulfonamides 3, 6 and 7 showed competitive inhibition. Conclusion: Use of drugs containing the sulfonamides molecule groups with crucial biological activity would be very dangerous in some cases. (C) 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.