Study of Drug Likeness of Praziquantel Derivatives for the Inhibition of Thioredoxin Peroxidase and Aspartic Protease in Opisthorchis Viverrini by Molecular Docking Method

This research aimed to study the effectiveness of eight praziquantel derivatives such as derivatives
substituted with -CH2(CH3)2 in R1 position (ligand G03_R1), -CH2CH2OCH3 in R1-R5 positions
(ligands G05_R1, G05_R2, G05_R3, G05_R4 and G05_R5) and -CH(NHCH3)(COOCH3) in R3
and R4 positions (ligands G17_R3 and G17_R4) as a drug for the inhibition of thioredoxin
peroxidase and aspartic protease in Opisthorchis viverrini by molecular docking method. It was
found that most derivatives could better interact with amino acids in the active site of both types of
enzymes than praziquantel. The ligand G03_R1 interaction with both types of enzymes was
similar to praziquantel. No interaction of ligands G17_R3 and G17_R4 in the active site of
thioredoxin peroxidase was found but they could best interact in the active site of aspartic protease.
The ligand G05_R3 could interact with both types of enzymes, and best interact with thioredoxin
peroxidase. The interaction energy value of -31.79 was obtained. -CH2CH2OCH3 group in ligand
G05_R3 bound with amino acids Ser148 and Glu151 in the active site by hydrophobic interaction
and the O1 and O33 atoms of this ligand could form hydrogen bonds with the amino acids Ile140
(N) and Thr139 (OG1). Furthermore, the interaction of ligand G05_R3 with aspartic protease was
similar to ligands G17_R3 and G17_R4 . The interaction energy value of -39.83 was obtained.
Therefore, it was concluded that the derivative, most suitable for development as a drug for
inhibiting thioredoxin peroxidase and aspartic protease, was the ligand G05_R3, a PZQ derivative
substituted with -CH2CH2OCH3 in R3 position.

Keywords: praziquantel derivatives, thioredoxin peroxidase, aspartic protease, Opisthorchis
viverrini, Molecular docking method

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E-mail: nusaijan@hotmail.com