Synthesis and docking studies of the functionalized dibenzylideneacetones as promising antimalarial agents

Context: First-line therapy using artemisinin-based combination therapy (ACT) and chloroquine in cases of malaria infection has developed resistance worldwide. Aims: To synthesize functionalized dibenzylideneacetones that are similar to curcumin and to perform the in silico evaluations on Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR) and through human dihydrofolate reductase (hDHFR) as targets for antimalarial agents. Methods: The functionalized dibenzylideneacetones were synthesized through a reaction of acetone with benzaldehydes in a base or acid catalyst. The resulting solids were purified by recrystallization to conduct UV/Vis, FTIR, and NMR tests. The confirmed products underwent an in silico molecular docking test on PfENR (PDB ID: 1NHG) and hDHFR (PDB ID: 1MVT). The products were obtained in good yields. Results: The confirmed products underwent in silico molecular docking test on PfENR (PDB ID: 1NHG) and hDHFR (PDB ID: 1MVT). The products were obtained with good yields. Based on in silico results, the dibenzylideneacetone was predicted to have a strong potential to inhibit the growth of malaria parasites through inhibit malaria growth through the PfENR pathway more than through the hDHFR pathway because its moldock score was lower than its native ligand. Conclusions: This study showed a promising pathway to obtain antimalarial agents for further application in the medical and pharmaceutical industries.