New benzoquinazoline derivatives as antitumor agents

DNA topoisomerases I and II are an actractive target for cancer treatment, because the inhibition of these enzymes trigger a chain of events causing cell death. Topoisomerase inhibitors, in fact, are among the most efficient inducers of apoptosis. To date, many dual topos inhibitors have been identified, with broader spectrum of activity in the respect of single enzyme inhibitors and active toward resistant. With the aim to find more efficient anticancer agents with dual antitopoisomerase activity, but also to find compounds useful to better elucidate the mechanisms on which topos activity is based, we designed and prepared a series of benzoquinazoline derivatives functionalized with dimethylaminoalkyl chains, using both conventional synthetic methodologies and microwave assisted organic synthesis. The preliminary screening on the ability to inhibit the cell growth showed interesting citotoxic activity for the new compounds. The ability of the compounds to exert their activity through DNA interactions, the study of their effects on the enzymatic activity of topoisomerase I and II and the effect of the tested compounds on the main parameters of mitochondrial functions will be evaluated and discussed in depth.