Project Abstract:

The present proposal is concerned with the development of new metal complexes based on a library of specifically modified indolo[2,3-c]quinolines and new indolo[3,2-d]benzazepines to be evaluated as anticancer drugs.
We propose to extend our studies on structure-activity relationships on these frameworks and to elucidate the effects of location of the lactam group in azepine ring, and orientation of indole basic unit with respect to quinolone-2-(1H)-one entity. The rationale behind our proposal is to design new metal complexes which can allow their application at very low doses due to the highly cytotoxicity, at nanomolar concentrations.
Thus the enormous potential impact of these new classes of metal-based drugs relies in their possible site-specific delivery in localized tumors, strongly improving their cellular uptake and minimizing unwanted side-effects, which could offer a significant advantage over platinum-based chemotherapeutics.