Atatürk University, Faculty of Science, Department of Chemistry, Erzurum, Turkey.
Istanbul Medeniyet University, Faculty of Engineering and Natural Sciences, Department of Chemistry, Istanbul, Turkey.
Pharmacol Rep. 2019 Jun;71(3):545-549. doi: 10.1016/j.pharep.2019.02.012. Epub 2019 Feb 20.
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.
Here, we report on the purification of the human serum PON1 using simple methods and determine the interactions between some sulfonamides and the enzyme.
We found that some sulfonamides exhibit potential inhibitor properties for the human serum PON1 with IC values in the range of 24.10-201.45 μM and K values in the range of 4.41 ± 0.52-150.23 ± 20.73 μM. 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.
Use of drugs containing the sulfonamides molecule groups with crucial biological activity would be very dangerous in some cases.
对氧磷酶 1（PON1）是一种抗动脉粥样硬化和有机磷水解酶。它具有重要作用，包括保护低密度脂蛋白（LDL）免受氧化和解毒高毒性物质。降低糖尿病、心血管疾病、甲状腺功能亢进症和慢性肾衰竭患者的这种酶的水平是一个主要的风险。
在这里，我们报告了使用简单方法对人血清 PON1 的纯化，并确定了一些磺胺类药物与该酶之间的相互作用。
我们发现一些磺胺类药物对人血清 PON1 具有潜在的抑制特性，IC 值在 24.10-201.45 μM 范围内，K 值在 4.41±0.52-150.23±20.73 μM 范围内。磺胺类药物表现出不同的抑制机制。我们确定磺胺类药物 1、2、4、5、8 和 9 表现出非竞争性抑制作用，而磺胺类药物 3、6 和 7 表现出竞争性抑制作用。
在某些情况下，使用含有磺胺类分子基团的具有关键生物活性的药物将非常危险。
