Synthesis and antimalarial activity of new 1,12-bis(N,N′-acetamidinyl)dodecane derivatives

Amidoxime and O-substituted derivatives of the bis-alkylamidine 1,12-bis(N,N′-acetamidinyl)dodecane were synthesized and evaluated as in vitro and in vivo antimalarial prodrugs. The bis-O-methylsulfonylamidoxime 8 and the bis-oxadiazolone 9 derivatives show relatively potent antimalarial activity after oral administration.

Graphical abstractAmidoxime and O-substituted derivatives of the bis-alkylamidine 1,12-bis(N,N′-acetamidinyl)dodecane were synthesized and evaluated as in vitro and in vivo antimalarial prodrugs. Among our compounds, the derivative bis-O-methylsulfonylamidoxime constitutes the best prodrug active on Plasmodium in vivo after oral administration.Figure optionsDownload full-size imageDownload as PowerPoint slide