Estudi de l’activitat biològica de compostos organometàl•lics com agents antitumorals vehiculitzats amb anàlegs de la Bombesina

Abstract

The prostate cancer (CaP) is between men the sixth cause of cancer death. The diverse treatments used against this neoplasm include mainly toxic effects on the organism, due to acting in both cancer cells and those that are normal. A new focus named “target delivery” tries to solve the problems of conventional treatments. Within therapies, one strategy involves joining antitumour agents to molecules that have an overexpressed receptor in cancer cells, to target them selectively. In prostate cancer cell line (PC3), the overexpressed receptor “Gastrin releasing peptide” (GRP) has been described, which presents as a ligand a peptide homolog to Bombesin, this one acts as a potent growth factor. The use of peptides derived from the Bombesin would carry antitumor agents specifically to PC3 cells. It has also been described that several organometallic complexes display antitumour activity depending on photoactivation, which would only allow active compounds on tumor cells when they are irradiated. The main objective of this study is the characterization of the biological activity of various organometallic compounds based on platinum and ruthenium, conjugated to an analogue peptide to the Bombesin. For this reason, its effect on the viability of prostate cancer cells has been studied, with the use of cell culture techniques. In addition, the ability of the different compounds to be photoactivated has been estimated, by means of its irradiation at λ = 447 nm. Based on the different techniques used, platinum L compound has been identified as a possible antitumor agent, due to its potent effect on cell viability. In addition, the ability of the ruthenium B complex to be photoactivable has been described, which would classify it as a non-toxic prodrug capable of exerting cytotoxic activity in a controlled way, from its irradiation. It has also been shown that the conjugation of the different compounds to a peptide analogue to the Bombesin and a sequence of nuclear localization (NLS), increase the internalization and activity of compounds in cancer cells. In addition, both peptides used as carriers can reach the nucleus; being the NLS sequence the cause of a greater accumulation at the nucleus of the compounds transported