Molecular Docking Studies and Inhibition Properties of Some Antineoplastic Agents against Paraoxonase-I.
BACKGROUND
Currently, most of the drugs used in clinical applications show their pharmacological influences by inhibiting or activating enzymes. Therefore, enzyme inhibitors have an essential place in the drug design for many diseases.


OBJECTIVE
The current study aimed to contribute to this growing drug design field (i.e., medicine discovery and development) by analyzing enzyme-drug interactions.


METHODS
For this reason, Paraoxonase-I (PON1) enzyme was purified from fresh human serum by using rapid chromatographic techniques. Additionally, the inhibition effects of some antineoplastic agents were researched on the PON1.


RESULTS
The enzyme was obtained with a specific activity of 2603.57 EU/mg protein. IC50 values for pemetrexed disodium, irinotecan hydrochloride, dacarbazine, and azacitidine were determined to be 9.63μM, 30.13μM, 53.31μM, and 21.00mM, respectively. These agents found to strongly inhibit PON1, with Ki constants ranging from 8.29±1.47μM to 23.34±2.71mM. Dacarbazine and azacitidine showed non-competitive inhibition, while other drugs showed competitive inhibition. Furthermore, molecular docking was performed using maestro for these agents. Among these, irinotecan hydrochloride and pemetrexed disodium possess the binding energy of -5.46 and -8.43 kcal/mol, respectively.


CONCLUSION
The interaction studies indicated that these agents with the PON1 possess binding affinity.
['Demir|Yeliz|Y|', 'Türkeş|Cüneyt|C|', 'Beydemir|Şükrü|Ş|']
D000970:Antineoplastic Agents D043303:Aryldialkylphosphatase D001374:Azacitidine D003606:Dacarbazine D004305:Dose-Response Relationship, Drug D015195:Drug Design D004791:Enzyme Inhibitors D006801:Humans D000077146:Irinotecan D062105:Molecular Docking Simulation D015394:Molecular Structure
molecular docking inhibition antineoplastic agent enzyme-drug interactions Paraoxonase chromatography