Abstract
Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: These drugs showed in competitive inhibition. Also, the molecular docking poses of these agents inside the catalytic sites of 1V04 and 3SRE were analysis.
Keywords: Paraoxonase, HDL, chromatography, inhibition, molecular docking, chemotherapeutic drug, protein-drug interactions.
Graphical Abstract
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