Three chalcone derivatives with amine groups (4a-c) were synthesized and evaluated for their antimalarial activity. Three aminoalkylated‒chalcone (4a-c) have been prepared through Claisen-Schmidt condensation reaction from vanillin and chloro-acetophenone, followed by Mannich reaction to add amine group. The structure of the compounds was confirmed by the spectrophotometric analysis using mass spectrometers (MS), proton and carbon nuclear magnetic resonance (1H- and 13C-NMR) spectroscopy. Antimalarial activity of 4a-c was evaluated against Plasmodium falciparum (3D7) strain and molecular docking of 4b was performed to understand the interaction against PfDHFR-TS protein (1J3I.pdb). The prepared aminoalkylated chalcone (4a-c) was obtained in a yield of 80, 75, and 70%. The addition of morpholine (4a), piperidine (4b), and diethylamine (4c) as amine groups significantly could improve the antimalarial activity with IC50 of 0.62, 0.54, and 1.12 µM respectively (strong activity), compared with the chalcone without amine group (3) with IC50 of 25.84 µM (moderate activity). The molecular docking of compound 4b exhibited strong hydrogen bonds interaction with ILE112, ILE64, SER111, SER108, ASP54, TYR170, AND PRO113 residues with CDOCKER interaction energy of -48.84 kcal/mol. Thus, aminoalkylated chalcone could be proposed for further studies and developing into antimalarial drug candidates.
Key words: Antimalarial, Chalcone, Docking, PfDHFR-TS,3D7
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