Drug design, chemical optimization and biological evaluation of pre-existing scaffolds towards selected therapeutic targets.

In this PhD thesis, I have focused my attention on drug design, chemical optimization and biological evaluation of pre-existing scaffolds towards selected therapeutic targets, such as UT-II receptor, tubulin and GSK-3beta. Firstly, I reported the synthesis of potential agonists and antagonists of UT-II receptor. These compounds share a monoketopiperazine scaffold, decorated with appropriate aminoacid residues that are pharmacophoric for UTR-II. Secondly, I presented the results about new 2-heterocyclyl-3-arylthio-1H-indoles as anticancer agents. Some derivatives exhibited potent tubulin assembly and cancer cell growth inhibition in vitro and in vivo assays. Thirdly, I showed the synthesis of new GSK-3beta inhibitors as potential anti-Alzheimer agents. New derivatives were obtained by chemical modification of a recently identified hit compound, leading to a potent GSK-3beta inhibitory activity in the low micromolar range of concentration.