Treatment of glioblastoma multiforme (GBM) is a formidable challenge. The intense investigation of numerous strategies to improve drug delivery in the context of GBM reflects the difficulty posed by the blood brain barrier (BBB), which provides both physical and biochemical barriers that limit penetration of most drugs into regions of invasive GBM.
The aim of the present research project is that to fully evaluate the potential of new ATI and ARDAP derivatives in glioblastoma treatment.
Preliminary results suggested that the replacement of the 3-methoxy group of the 3,4,5-trimethoxy portion with the bromine atom boost both inhibition of tubulin polymerization and anticancer activity. Aims of the present research project are: 1. design of the new compounds and molecular modelling studies; 2. chemical synthesis of the most promising compounds; 3. biological evaluation of the newly prepared compounds as inhibitors of tubulin polymerization and [3H]colchicine binding; 4. further biological characterization of the selected compounds in glioblastoma cells; 6. in vitro and in vivo pharmacokinetic characterization of the selected compounds.
The final goal of the present research project is the identification of one or more lead compounds with potent anti-glioblastoma activity and improved pharmacokinetic profile for the treatment of glioblastoma patients.