Targeting Plasmodium falciparum: Synthesis and evaluation of Phthalimide-HEA derivativesChemical Biology Letters​

Articles, Hydroxyethylamine, Phthalimide, Malaria, Molecular Docking, Synthesis

We demonstrated a facile microwave-assisted synthesis of 16 novel phthalimide (Pht)-hydroxyethylamine (HEA)-based compounds isolated without tedious column chromatography. Among all the tested compounds, 3b, 3f, and 3h displayed 50% inhibitory concentration in the micromolar range (0.17 – 1.60 µM) against the Pf3D7 strain. Of particular note, compound 3f showed the highest potency with an IC₅₀ value of 0.17 ± 0.001 µM. Further, stage-specific assay revealed that hit 3f was predominantly active at the ring stage. None of the compounds exhibited marked cytotoxicity up to 500 µM concentration on HepG2 liver cells. Further, preliminary computational studies suggested that aminopeptidase N could be the potential target for hit 3f, which needs to be validated through enzymatic assays.

We demonstrated a facile microwave-assisted synthesis of 16 novel phthalimide (Pht)-hydroxyethylamine (HEA)-based compounds isolated without tedious column chromatography. Among all the tested compounds, 3b, 3f, and 3h displayed 50% inhibitory concentration in the micromolar range (0.17 – 1.60 µM) against the Pf3D7 strain. Of particular note, compound 3f showed the highest potency with an IC50 value of 0.17 ± 0.001 µM. Further, stage-specific assay revealed that hit 3f was predominantly active at the ring stage. None of the compounds exhibited marked cytotoxicity up to 500 µM concentration on HepG2 liver cells. Further, preliminary computational studies suggested that aminopeptidase N could be the potential target for hit 3f, which needs to be validated through enzymatic assays. 

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Chemical Biology Letters