Chemical drugs.

Study on the expression of pepper (Capsicum annuum L.) genes and their pharmacological applications: Quercetin – Verónica Ruiz Trujillo

2 May, 2022 por Anabel Torrente Leave a Comment

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.

Keywords: Pepper; nitric oxide (NO); quercetin; flavonoid compounds.

Directed by: José Manuel Palma Martínez

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

Desing, synthesis and biological evaluation of choline kinase enzyme inhibitor diazufro derivatives – Marina Úbeda García

1 May, 2022 por Anabel Torrente Leave a Comment

In this research, a total of 9 symmetrical diazuffered bis-cationic compounds with inhibitory activity against the human ChoKα1 enzyme were designed, synthesised and characterised. The aim was to find compounds with effective inhibitory and antiproliferative activity in tumour cells. In-vitro biological assays were performed to determine their capacity to inhibit human ChoKα1 and restrict its proliferation. We noted that slight changes in the structure of the molecules give rise to considerable variations in inhibitory activity and antiproliferative capacity and that compounds with a high capacity to inhibit the enzyme were unable to inhibit tumour cell development and vice versa. Further studies are therefore needed to investigate the mechanism of action, as well as to continue in-vitro synthesising and testing of new ChoKα1 inhibitor compounds, so as to find molecules that perform this function successfully.

Keywords: sulphur derivatives; inhibitory capacity; antiproliferative capacity; choline kinase.

Directed by: Luisa Carlota López Cara

Cocrystals for the improvement of the physicochemical properties of the anti-inflammatory drug etenzamide – Ángel Ibáñez Gijon

30 April, 2022 por Anabel Torrente Leave a Comment

The aim of this Master’s Thesis is to obtain new multicomponent pharmaceutical solids containing the active ingredient etenzamide, which belongs to the therapeutic group of non-steroidal anti-inflammatory drugs (NSAIDs), in order to improve its solubility and therefore its oral bioavailability. For this purpose, we selected the 6 co-formers most likely to form a cocrystal with this active ingredient, namely Hydroquinone (HQ), Catechol (CAT), Resorcinol (RES), Pyrogallol (PYR), Phloroglucinol (FLU) and Orcinol (ORC). The new solids were synthesized by mechanochemical synthesis and characterised by Powder X-ray Diffraction (PXRD), Single Crystal X-ray Diffraction (SCXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and Thermogravimetry (TGA). Solubility studies were conducted as were tests on stability when exposed to humidity and heat. The results obtained were very promising, since all the ethenzamide cocrystals showed an improvement in solubility compared to the active ingredient.

Keywords: multicomponent pharmaceutical solid; pharmaceutical cocrystal; etenzamide; NSAIDs; solubility

Directed by: Alicia Dominguez Martín