Investigation of Potential Paraoxonase-I Inhibitors by Kinetic and Molecular Docking Studies: Chemotherapeutic Drugs

Protein and Peptide Letters
Cüneyt Türkeş

Abstract

Metabolic processes in living organisms are closely related to the catalytic activity of enzymes. Changes in enzyme activity cause various diseases e.g., neurological, cancer, metabolic and cardiovascular. Most of the current therapeutic drugs available in clinical utilization function as enzyme inhibitors. The main goal of the current study to contribute to this growing drug design area (such as medication discovery and development) by investigating protein-drug interactions. The paraoxonase-I (PON1) enzyme was purified from human serum by using different and simple chromatographic techniques. Additionally, it was investigated inhibition effects of some chemotherapeutic drugs on the PON1. The purification results for PON1 depicted a 3880.83 EU/mg proteins specific activity and the molecular weight was calculated as 43 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These drugs found to strongly inhibit PON1, with IC50 values ranging from 0.222±0.002 to 688.300±0.897 µM. Ki constants for vincristine sulfate, epirubicin hydrochloride, and doxorubicin hydrochloride were determined to be 0.235±0.032 µM, 221.400±29.270 µM, and 913.300±201.000 µM, respectively. These drugs showed in competitive inhibition. Also, th...Continue Reading

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Citations

Jun 11, 2019·Drug and Chemical Toxicology·Şükrü BeydemirAhmet Yalçın
Aug 28, 2019·Journal of Biochemical and Molecular Toxicology·Cüneyt Çağlayanİlhami Gulçin
Feb 29, 2020·Journal of Biomolecular Structure & Dynamics·Cüneyt TürkeşŞükrü Beydemir
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Jul 26, 2019·Applied Biochemistry and Biotechnology·Cüneyt Türkeş, Şükrü Beydemir
Aug 14, 2020·Journal of Biomolecular Structure & Dynamics·Cüneyt TürkeşŞükrü Beydemir
Apr 7, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Mustafa DurgunClaudiu T Supuran
Mar 16, 2021·Journal of Biomolecular Structure & Dynamics·Mouhi Eddine HachimMy Youssef Ait Itto
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Nov 2, 2020·Seminars in Cancer Biology·Shiva GanjaliAmirhossein Sahebkar
Aug 24, 2021·Journal of Biomolecular Structure & Dynamics·Yeliz DemirŞükrü Beydemir
Nov 18, 2021·Biotechnology and Applied Biochemistry·Büşra ÇalışkanCüneyt Türkeş

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