Melanny Ika Sulistyowaty, Galih Satrio Putra, Tutuk Budiati, Anastasia Wheni Indrianingsih, Yunita Wahyu Renawanti, Kholis Amalia Nofianti, Juni Ekowati, Neny Purwitasari, Charinrat Saechan, Sabry A.H. Zidan, Takayasu Yamauchi
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. © 2025 Journal of Pharmacy & Pharmacognosy Research.
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia; School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, Japan; Department of Chemistry, Faculty of Mathematics and Natural Sciences, State University of Malang, Malang, Indonesia; Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, Indonesia; Research Center for Food Technology and Processing, National Research Innovation and Agency (BRIN), Gunung Kidul, Yogyakarta, Indonesia; Faculty of Medical Technology, Prince of Songkla University, Songkhla, Thailand; Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
