Cáncer

Design and study of new drugs with possible antitumor activity – Noelia Ruiz Cuevas

8 May, 2022 por Anabel Torrente Leave a Comment

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

Use of nanotechnology to transport dugs in the body – Pablo Nevado López

7 May, 2022 por Anabel Torrente Leave a Comment

Various different therapeutic strategies are applied against cancer, such as chemotherapy, radiotherapy, immunotherapy and the different combinations between them. Pharmaceutical nanotechnology is a science that has long been applied in the preparation of drug delivery vehicles. Many interesting innovations and therapeutic applications have emerged in recent years. The purpose of these systems is to protect the drug (or active ingredient), modify some of its characteristics and improve its distribution in body cells, among others.

In this study, we propose to design a new drug transport system on a nanometric scale. To this end, nanoparticles made up of two layers of polymers (chemical compounds) were designed. This multilayer is made of PLGA (poly(D,L-lactide-co-glycolide) and coated with chitosan. The nanoparticles contain an active ingredient called 5-Fluorouracil, which is classified as a cytostatic and is used to treat cancer.

Keywords: Pharmaceutical nanotechnology; cancer; drug delivery system, polymers, 5-Fluorouracil.

Work directed by: Margarita López-Viota Gallardo

Quantitative stability analysis of nivolumab, an anti-tumour drug – Lorena Jiménez Morán

7 May, 2022 por Anabel Torrente Leave a Comment

Cancer, which involves an uncontrolled increase in cell proliferation and growth, remains one of the leading causes of death worldwide. Our immune system tries to eliminate this excess proliferation of cells from the body. However, cancer has mechanisms that help it evade the actions of the immune system, making it very difficult to fight effectively.
New therapies and drugs are being developed to combat this disease. One such drug is nivolumab, which is used to treat lung cancer, among others. However, it has an important disadvantage in terms of its high price and its loss of efficacy in certain storage conditions or during hospital use, because of its protein nature. In this project a quantitative technique (MicroScale thermophoresis) is used to analyze the efficacy and stability of nivolumab over time and when subjected to conditions similar to those applicable during handling of the drug in hospitals.

Keywords: cancer; nivolumab; efficacy; stability; MicroScale thermophoresis

Directed by: Jesús Hermosilla Fernández

Designing new drugs for the treatment of cancer – Laura Erviti Marticorena

7 May, 2022 por Anabel Torrente Leave a Comment

CD44 is a protein that is found on the surface of human cells. It interacts with another protein, hyaluronic acid (HA), causing normal cells to become tumour cells, so enabling tumour development, metastasis and resistance to drug treatment. HA-CD44 interaction is therefore an interesting pharmacological target in cancer therapy.
The main objective of this project is the design, synthesis, and biological evaluation of inhibitors of HA-CD44 interaction, known as derivatives of 1,2,3,4-tetrahydroisoquinoline (THIQ). These molecules act as antitumor agents because they bind to CD44 in a place close to where HA binds, thus inhibiting HA-CD44 interaction. To this end, in this project we study the influence of small variations in the structure of 1,2,3,4-tetrahydroisoquinoline on the inhibition of the HA-CD44 interaction.

Keywords: cancer; inhibitors; hyaluronic acid; CD44, isoquinoline.

Directed by: Ana Conejo García

Synthesis, purification and structural determination of isoquinolin-5-ol derivatives as antitumor agents – Soledad Romero Tamudo

1 May, 2022 por Anabel Torrente Leave a Comment

Cancer is a disease that begins when a cancerous cell manages to evade the main regulatory mechanisms of the cell cycle and begins to proliferate uncontrollably. It is one of the leading causes of death worldwide, so the search for new therapies is essential.
CD44 is a glycoprotein whose increased expression makes tumors more resistant to cancer treatments. Its ligand is hyaluronic acid (HA) and after binding, signaling cascades are activated that contribute to increased cell proliferation, migration and tissue invasion.
Tetrahydroisoquinoline (THIQ) inhibits binding between CD44 and HA. With this in mind, in this Master’s Thesis, we propose the synthesis of 10 isoquinolin-5-ol derivatives. We will then assess the capacity of these derivatives to act as antitumor agents by inhibiting binding between CD44 and HA.

Keywords: Cancer; CD44; Hyaluronic Acid; Tetrahydroisoquinoline; Inhibitors.

Directed by: María Dora Carrión Peregrina