CD44 is a membrane receptor found in various types of cells in our body. This receptor binds mainly to hyaluronic acid (HA). The interaction of HA with CD44 induces changes that trigger rapid growth (proliferation) of cancer cells. Inhibition of this interaction could therefore interrupt tumour progression.
There is a specific place (small pocket) in the structure of CD44 in which small molecules could be introduced that would act as inhibitors of tumour activity. The first structures to show inhibitory activity when interacting with this pocket were molecules known as tetrahydroisoquinoline derivatives. However, it is difficult to assess the capacity of these molecules as possible antitumor agents due to their poor solubility. The main objective of this research is therefore to synthesize a series of isoquinoline salts that have good solubility in water, so facilitating the biological evaluation of these molecules.
These molecules are obtained via the reaction of isoquinoline with a chemical compound, the 3,4,5-trimethoxybenzyl group, and the introduction of different substituents in its structure, specifically in a structure known as an aromatic ring. These substitutions enable us to study the structure-activity relationship and the effect on the binding of the molecules to the aforementioned pocket in CD44.
Keywords: cancer; inhibitors; hyaluronic acid; CD44; isoquinoline.
Directed by: Olga Cruz López
This research was carried out in the Antioxidants, Free Radicals and Nitric Oxide in Biotechnology and Agri-Food Research Group (Zaidín Experimental Station, CSIC, Granada). In recent years, this group has been investigating the possible contribution that peppers can make to a better state of health, thanks to the fact that they contain compounds of pharmacological and therapeutic interest. In collaboration with the University of Malaga and the MEDINA Foundation, we conducted metabolomic and transcriptomic studies to analyse a series of metabolic pathways that lead to the synthesis of molecules with this potential capacity. These molecules are also modulated by nitric oxide (NO), a molecule whose functions in the physiology of both animal and plant cells are increasingly recognised. This Master’s Thesis takes a step further in this strategy which, together with other metabolomic data recently obtained, has allowed the group to focus its research on quercetin, one of the flavonoid compounds present in peppers, which has a number of pharmacological properties.
