Synthesis, characterization, docking study and biological evaluation of new chalcone, pyrazoline, and pyrimidine derivatives as potent antimalarial compounds

Abstract Malaria is a protozoan disease caused by a unicellular parasite named Plasmodium (Phylum- Apicomplexa). World Health Organization has estimated roughly fifty percent of the world’s community lives under the continuing threat of malaria. The focus of drug discovery has increased towards valuable structures known as chalcones, pyrazoline, and pyrimidine due to their extensive bioactivity in malaria treatment. In this study, four chalcone derivatives (1–4) have been synthesized via the Claisen-Schmidt condensation. New compounds of 12 pyrazolines (1–4)Ai-iii and eight pyrimidines, (1–4)Bi-ii derivatives have also been synthesized via a ring-closing reaction of the chalcones. All the synthesized compounds were characterized and tested against malaria. The results showed that compound 1Aiii exhibited significant antiproliferative effects against 3D7 and RKL9 with 3D7 = 2.1 μg/mL, IC80 3D7 = 8 μg/mL, and IC50 RKL9 when exposed to compared to the reference anticancer drug, CQ Chloroquine diphosphate, and Artemisinin. The molecular docking analysis showed that compounds 1, 1Aiii and 1Bi had entered the PfATP4 receptor pocket and had been stuck with the amino acids in a high affinity of binding.