Synthesis and antimalarial evaluation of a series of piperazinyl flavones

A series of 27 flavonoid derivatives containing a piperazinyl chain have been synthesized and tested for their antiplasmodial activity. Diverse substitution patterns on piperazinyl and flavone moieties were examined and found to affect the activity differently. The most active compounds, which have a 2,3,4-trimethoxybenzylpiperazinyl chain attached to the flavone at the 7-phenol group, showed in vitro activity against chloroquine-sensitive (Thai) and -resistant (FcB1, K1) Plasmodium falciparum strains in the micromolar to submicromolar range. One of them was active when given orally in a Plasmodium yoelii nigeriensis infected mouse model.

Graphical abstractMost of 27 synthesized piperazinyl flavones displayed micromolar in vitro inhibition of Plasmodium falciparum, including 1 also active when given orally to Plasmodium yoelii nigeriensis infected mice.Figure optionsDownload full-size imageDownload as PowerPoint slide