Study of Pt(II) and Pt(IV) derivatives, functionalized with antitumor active principles: Multitarget anticancer agents with several action mechanisms

Abstract

Over the past 50 years, antitumor platinum complex such as cisplatin oxaliplatin and carboplatin have played relevant roles in the treatment of solid tumors. However, many side effects, drug resistance and poor selectivity limit their application encouraging the search for new platinum-based antitumor drugs with new and more effective action mechanisms. In this final degree project, a bibliographic research is carried out of the most novel platinum antitumour complexes, as well as their mechanisms of action and strategies. We also investigate a method of drug monitoring using a conjugated fluorescent probe. The search for information was carried out mainly with the SciFinder platform and using the University's access to a multitude of scientific journals. After this search, the most relevant information obtained was selected, organized and synthesised. The idea of conjugating several biomolecules with a specific anticancer activity to the platinum complex provides several anticancer mechanisms acting simultaneously improving the efficiency and the selectivity of platinum antitumour complexes against cancer cells versus normal cells, and may bypass the resistance of cancer cells. Concerning the strategy, we envision the possible application of multitarget Pt(IV) complexes as prodrugs instead of the classical Pt(II) ones. They are more stable, thus avoiding undesired reactions.They can also carry on more ligands than Pt(II) complexes, increasing the possibilities to combine different mechanisms of action or to combine them with ligands that increase their specificity and thus reducing toxicity. For the study and monitoring of such complexes, fluorescence testing is being used, which is a technique capable of distinguishing the oxidation state of platinum as well as being able to track its location within the cell or the specific target tissue and organ in the body.