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.