Ricerc@Sapienza

The purpose of this research proposal is the design, the synthesis and the biological evaluation of new anticancer drugs by tubulin binding at the colchicine site. This research group already reported 3-Aroyl-1-arylpirroles (ARAPs) derivatives featured by anti-proliferative activity at nanomolar concentration in a short panel of cancer cell lines. These promising results encouraged us to improving our ARAPs structure activity relationships knowledge. Since, it is well known the pharmacophoric role of the trimethoxy group we will manage the chemical modification of the N-1 pyrrole position by the aryl moiety substitution with five and six member heteroaromatic rings. The new designed ARAPs derivatives will be evaluated by molecular modelling studies to clarify the binding mode at the cochicine site and to prioritize the synthesis of the new derivatives. All the newly synthesized compounds will be tested with the aim to measure their ability to impair tubulin polymerization, binding at the colchicine site as well as MCF-7 human breast carcinoma cell growth inhibition.