Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Minandre Wiratama, Stephanus Satria Wira Waskitha, Winarto Haryadi, Tutik Dwi Wahyuningsih

Department of Chemistry, Universitas Gadjah Mada, Sekip Utara, Bulaksumur, 21, 55281, Yogyakarta, Indonesia;

For correspondence:- Tutik Wahyuningsih Email: tutikdw@ugm.ac.id Tel:+62818467863

Accepted: 24 May 2022 Published: 30 June 2022

Citation: Wiratama M, Waskitha SS, Haryadi W, Wahyuningsih TD. Synthesis, antimalarial activity assay and molecular docking study of N-substituted chloro-pyrazolines. Trop J Pharm Res 2022; 21(6):1255-1261 doi: 10.4314/tjpr.v21i6.18

© 2022 The authors.
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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.

Keywords: Pyrazoline, Antimalarial, Docking Simulation, Plasmodium falciparum 3D7