Synthesis, antimalarial activity assay and molecular docking study of N-substituted chloro-pyrazolines

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.