ABSTRACT
Three chalcone derivatives with amine groups (4a–c) were synthesized and evaluated for their antimalarial activity.Three aminoalkylated chalcone derivatives (4a–c) have been prepared through Claisen–Schmidt condensation reactionfrom vanillin and chloroacetophenone, followed by the Mannich reaction to add amine group. The structure of thecompounds was confirmed by the spectrophotometric analysis using mass spectrometers (MS) and proton and carbonnuclear magnetic resonance (1H- and 13C-NMR) spectroscopy. Antimalarial activity of 4a–c was evaluated againstPlasmodium falciparum (3D7) strain, and the molecular docking of 4b was performed to understand the interactionagainst Pf DHFR-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 significantlycould improve the antimalarial activity with IC50 of 0.62, 0.54, and 1.12 µM, respectively (strong activity), comparedwith the chalcone without amine group (3) with IC50 of 25.84 µM (moderate activity). The molecular docking ofcompound 4b exhibited strong hydrogen bond interaction with ILE112, ILE64, SER111, SER108, ASP54, TYR170,and PRO113 residues with CDOCKER interaction energy of −48.84 kcal/mol. Thus, aminoalkylated chalcone couldbe proposed for further studies and developed into antimalarial drug candidates