Novel fluorinated piperazine based-amino acid derivatives as antiplasmodial agents: Synthesis, bioactivity and computational studies
Keywords:Plasmodium falciparum, anti-malarial drugs, heteroaromatic amino acid, antimalarial agent, in-silico studies
A library of twenty novel analogues of fluorinated, N-(3-hydroxy-1-phenyl-4-(4-phenylpiperazin-1-yl)alkyl)amides containing different amino acids were synthesized and tested for the activity against Plasmodium falciparum (Pf3D7) culture. All the tested compounds showed TC50 values >100 µM on HepG2 cells. Hit analogues 12c and 12e, displayed IC50 values in the sub-micromolar range, i.e., 0.696±0.0462 µM and 0.9377±0.0461 µM, respectively. Compounds 12c and 12e were also evaluated in combination with artemisinin, which slightly improved the activity of both the compounds with IC50 values of 0.19 µM and 0.26 µM, respectively. For compounds 12c and 12e, in-silico studies were carried out. Overall, results obtained from both in vitro and in-silico studies, indicated that 12c and 12e were hit compounds with maximum potency.