Synthesis and Cytotoxic Activity of Isoacronycine and Its Derivatives

Condensation of N-methyl-1,3-dihydroxyacridone with 3-methyl-2-butenal led selectively to norisoacronycine, which upon methylation gave isoacronycine. Functionalization of the 1,2 double bond of isoacronycine led to derivatives with reduced cytotoxicity compared with the corresponding ones deriving from acronycine. Two very interesting exceptions were 1-hydroxy-1,2-dihydroisoacronycine (14) and its acetate (16), which showed strong induction of apoptosis.