| Popis: |
The synthesis of novel hybrid materials, combining the properties of organic and inorganic components in one compound, results in materials with unique physical and chemical properties. Currently, medicinal chemists are looking for new hybrid materials which have high bioactivity and specificity, and present low health and safety risks. Polyoxometalates are inorganic metal oxo-clusters and important drug candidates with remarkable antiviral, antibacterial, and antitumoral activities. One key advantage of anionic polyoxometalates (POMs) is that a functional cation can easily be introduced as a second reactive component to afford multifunctional compounds. Herein, the ionic self-assembly between the organic-based cations and the anionic polyoxometalates leads to the formation of well-defined multivalent composites. Derivatization of POMs with organic partners, including synthetic molecules and natural bio-bases, is expected to result in a synergetic effect and endow the POM hybrid with novel functions or properties. Understanding the mechanism and timing of interaction of organic-POMs materials with multiple biomolecule targets in a single event or different processes simultaneously in the biological systems, will provide a basis for the development of a novel field for drug discovery. This dissertation is about the design and synthesis of novel polyoxometalate-based ionic materials towards antibacterial, antimicrobial and antitumoral applications. The characterization, analysis of their pharmacokinetics properties, mechanism of action, therapeutic potential and future clinical directions will be presented. Chapter I contains an extensive introduction to the class of POMs and their organic derivatives which presents bioactivity against pathogenic microorganisms. The following chapters explain the mode of action of these compounds from the results of in vitro analysis. Generally, this mechanism might not be explained by one strict mechanism with one single target but rather by multiple POM-protein interactions affecting several biological pathways at the same time and the sum of these disturbances ultimately leads to the bioactivity. Chapter II describes the synthetic procedures for a novel POM-IL and its support on a polymer matrix in order to prepare films with antibacterial and antifungal activities. Chapter III comprises the antiviral activity of POMs divided in two sections. The first section is related to the synthesis of a hybrid material based on a caffeinium cation and a lanthanide containing polyoxotungstate, and its anti-HIV activity. It has been optimized by adding the organic partner in order to increase cell specificity and targeted delivery to avoid the toxic side effect of polyoxometalates. The second section presents the anti-ZIKV activity of POMs by computational methods and in vitro approach. These results would contribute both to the design of alternative antiviral therapies and to the knowledge of the mechanism of action of polyoxometalates as antiviral agents. Chapter IV presents the conclusions. Access to pure POM-based organic bio-based hybrid materials is particularly attractive as they can combine high-cluster loadings with unique properties that open the door to an enhanced field of biological applications. The synthesis and potential applications of these compounds as antiviral, antibacterial and antifungal compounds are expected to highlight the impact of POM-organic materials science and enrich the field of medicinal chemistry. |
