Synthesis and In Vitro Antimalarial Activity of Amino Chalcone Derivative Compounds by Inhibition of Heme Polymerization

Abstract

This study investigated the potential of chalcone derivatives as antimalarial agents. The structures of the chalcone derivatives were designed by including amino substituents on acetophenone and methoxy variants on benzaldehyde. As a result, three amino chalcone derivatives (1-3) were synthesized. The synthesis was conducted by performing the Claisen-Schmidt condensation reaction with 40% NaOH as the base catalyst, resulting in a yield ranging from 66% to 83%. In addition, the structures of the compounds were determined by FTIR, MS, and 1H-NMR spectroscopy techniques, confirming that the compounds possess structures that align with the desired molecular structure. The antimalarial activity test was conducted by inhibiting the process of heme polymerization into hemozoin (β-hematin) in a controlled laboratory setting. This process is one of the key targets of antimalarial medication therapy. Among the compounds, compound 2 exhibited superior antimalarial activity, with an IC50 value of 118.15 μg/mL, in comparison to the positive control hydroxychloroquine sulphate (IC50 value of 184.98 μg/mL). The inhibitory action of heme polymerization in the synthesis of hemozoin was influenced by the location and quantity of methoxy groups in the chalcone molecule, as observed in this work.