Targeted Therapy to Fight Cancer: Design, Synthesis, and Functional Evaluation of Novel Small Molecules

During my Ph.D. research period, I’ve been involved in different aspects concerning cancer, including the understanding of mechanisms behind its etiopathogenesis and the development of novel drug candidates to fight it. Cancer indeed is a group of diseases very challenging to treat, altogether representing the second leading cause of death globally. [1] The main problem concerning cancer is the fact that it originates from normal body’s cells which start to proliferate uncontrollably. [2] For this reason, targeting cancer cells without affecting the normal ones, has become one of the biggest challenges for the researchers. In my research work, I approached this problem from different angles. My main occupation, as a medicinal chemistry researcher, was the design and synthesis of small molecules as modulators of receptors or enzymes involved in cancer pathogenesis. Secondly, I was involved in the biological evaluation of small molecules, carried out on both purified enzymes and cellular models. Lastly, I investigated the problem of drug delivery. Actually, it doesn’t matter how good a drug is in the in vitro tests if it couldn’t reach its target in vivo. In this thesis manuscript I will cover all the aspects I worked on during my research period, starting from the modulation of different targets for the treatment of cancer, classifying them in traditional and innovative: • Traditional targets o Tyrosine kinases (TKs) • Innovative Targets: o Cancer stem cells (CSCs) o AMP-activated protein kinase (AMPK) o Aldose reductase (ALR2) Moreover, a part of this manuscript will be dedicated to new drug delivery systems.