Synthesis and Preliminary Biophysical and Cellular Evaluation of Some Ring-Enlarged Analogues of the Anti-Tumor Plant Alkaloid Acronycine

Three oxepinoacridine analogues of the important anti-cancer pyranoacridine natural product acronycine have been synthesized using a combined Claisen rearrangement ring-closing metathesis sequence as key steps to install the oxacyclic ring. Preliminary biophysical studies of these proposed oxepino analogues revealed that they interact with ct-DNA in a manner similar to the pyranoacridones but not possibly as intercalators. Cellular evaluations of these analogues in two human leukemic cell lines have also been carried out. These studies indicate that the ring-enlarged analogues have somewhat lower activity than the naturally occurring ones in the cell lines studied.