| Abstrak/Abstract |
Purpose: To synthesize chloro-pyrazolines (A–D), determine their antimalarial activity against
Plasmodium falciparum strain 3D7 in vitro, and understand the interaction between falcipain-2 active
sites and synthesized compounds by molecular docking simulation.
Methods: Chloro-pyrazolines (A–D) were synthesized via cyclo-condensation of 4-chloro chalcone
derivatives using several types of hydrazines, i.e., formylhydrazine, benzoylhydrazine, phenylhydrazine
and chlorophenylhydrazine. The compounds were analyzed and subjected to antimalarial assay against
P. falciparum 3D7. Molecular docking was performed using AutoDock Tools and AutoDock Vina, while
each docked compound was visualized using Discovery Studio Visualizer.
Results: Pyrazolines A–D yield was 87.09, 61.71, 50.24 and 57.64 %, respectively. Antimalarial assay
showed half-maximal inhibitory concentration (IC50) values of 16.46 and 5.55 µM for pyrazoline A and B,
respectively, and ≥ 100 µM for pyrazoline C and D. Molecular docking study revealed that pyrazolines
A–D had good interaction with the active site of falcipain-2 receptor.
Conclusion: A series of N-substituted chloro-pyrazolines has successfully been synthesized with
moderate yield. Pyrazoline B has the highest antimalarial activity against P. falciparum 3D7 with IC50 of
5.55 µM. This finding is supported by molecular docking and indicates that the benzoyl substituent
increases the antimalarial activity of pyrazoline B. Pyrazoline B has potentials for clinical application as
an antimalaria agent. |
