Synthesis of febrifugine derivatives and development of an effective and safe tetrahydroquinazoline-type antimalarial

•Febrifugine (1) isolated from Dichroa febrifuga shows potent antimalarial activity.•The antimalarial potential of synthetic derivatives of 1 was published in our previous work.•More derivatives of 1 were synthesized and evaluated.•Tetrahydroquinazoline-type derivative 5 is an effective and safe antimalarial candidate.

Febrifugine, a quinazoline alkaloid isolated from Dichroa febrifuga roots, shows powerful antimalarial activity against Plasmodium falciparum. Although the use of ferifugine as an antimalarial drug has been precluded because of its severe side effects, its potent antimalarial activity has stimulated medicinal chemists to pursue its derivatives instead, which may provide valuable leads for novel antimalarial drugs. In the present study, we synthesized new derivatives of febrifugine and evaluated their in vitro and in vivo antimalarial activities to develop antimalarials that are more effective and safer. As a result, we proposed tetrahydroquinazoline-type derivative as a safe and effective antimalarial candidate.

Graphical abstractNew derivatives of febrifugine were synthesized, and their in vitro and in vivo antimalarial activities were evaluated. As a result, we proposed tetrahydroquinazoline-type derivative 5 as a safe and effective antimalarial candidate.Figure optionsDownload full-size imageDownload as PowerPoint slide