23 resultados para doxorubicin derivative


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Dissertação para obtenção do Grau de Mestre em Biotecnologia

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J Biol Inorg Chem (2010) 15:409–420 DOI 10.1007/s00775-009-0613-6

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A PhD Dissertation, presented as part of the requirements for the Degree of Doctor of Philosophy from the NOVA - School of Business and Economics

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Dissertação para obtenção do Grau de Doutor em Química Sustentável

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Review article Martins, P., Marques, M., Coito, L., Pombeiro, A.J.L., Baptista, P.V., Fernandes, A.R. 2014. Organometallic Compounds in Cancer Therapy: Past Lessons and Future Directions. Anti-cancer Agents in Medicinal Chemistry 14. PMID: 25173559

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Cancer is a well-known disease with a significant impact in society not only due to its incidence, more evident in more developed countries, but also due to the expenses related to medical treat-ments. Cancer research is considered an increasingly logical science with great potential for the development of new treatment options. Advances in nanomedicine have resulted in rapid devel-opment of nanomaterials with considerable potential in cancer diagnostics and treatment. The combination of diagnosis and treatment in a single nano-platform is named theranostic. In this PhD thesis a theranostic system for osteosarcoma was proposed, composed by a magnetic core, a polymeric coating, and a chemotherapeutic drug. The presence of a specific targeting agent, in this case a monoclonal antibody, provides high specificity to the proposed theranostic system. For the core of the proposed theranostic system, stable aqueous suspensions of superparamagnetic iron oxide nanoparticles with an average diameter of 9 nm were produced. Chitosan-based poly-meric nanoparticles with a hydrodynamic diameter around 150 nm were successfully produced. Incorporation of iron oxide nanoparticles into the polymeric ones increased their hydrodynamic diameter to at least 250 nm. A monoclonal antibody specific for a transmembranar protein (car-bonic anhydrase IX) present in solid tumors was developed by hybridoma technology. Functional hybridomas producing the desired monoclonal antibodies were obtained. The proposed theranostic system functionality was evaluated in separated parts of its components. Uncoated and coated iron oxide nanoparticles with chitosan-based polymers generated heat under the application of an external alternating magnetic field. Uncoated iron oxide nanoparticles sta-bilized with oleic acid were able to enhance contrast in magnetic resonance imaging. Drug deliv-ery studies were conducted in chitosan-based polymeric nanoparticles without and with the in-corporation of iron oxide nanoparticles, demonstrating to be an effective drug delivery platform for doxorubicin. The theranostic system proposed in this PhD thesis is very promising for cancer theranostic, demonstrating to be applicable in solid tumors such as osteosarcoma.

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The aim of this work was to study the self-assembly process of C3-symmetric molecules. To accomplish this objective 1,3,5 – benzentricarboxamides (BTA) derivatives were obtained. Five C3-symmetric molecules were synthesized in moderate to good yields (39-72%) using azo-benzene, aniline, benzylamine, tryptophan and tyrosine. The aggregation behavior of the BTA derivatives was probed with 1H-NMR spectroscopy, 1H-1H 2D Nuclear Overhauser Effect Spectroscopy (NOESY) and Diffusion Ordered Spectroscopy (DOSY). These experiments allowed to study the influence of H-bonding groups, aromatic rings, unsaturated bonds and the overall geometry in the molecular self-assembly associated with the different structural patterns present on these molecules. The stacking and large molecule behavior where observed in BTA 1, aniline derivative, BTA 4, tyrosine derivative or BTA 5, tryptophan derivative, with several of those discussed functional groups such as unsaturated bonds and H-bonding groups. BTA 5 was used in a few preliminary interaction studies with glucose and ammonium chloride showing interaction with the ammonium ion.

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This master thesis has been developed during the internship in the Supervision Department of Supervision of the Intermediation and Market Structures of CMVM. My collaboration in such department was mainly focused on the derivatives market of the Iberian Electricity Market (MIBEL). MIBEL embodies two organized markets – the derivatives market in Portugal and the spot market in Spain The trading activity in the derivatives market of MIBEL is processed through the trading platform of the regulated market managed by OMIP, however, much of the negotiation is over-the-counter. The aim of this work is to describe the market from a legal and economic perspective and to analyse the evolution of the negotiation, namely the impact of OTC in the regulated market trading. To achieve this, I propose to analyse also MiFID and EMIR rules over derivative contracts and the role of central counterparties, as they both are important to the discussion. In parallel, we found that OTC transactions are considerably higher than those traded in the regulated market managed by OMIP, those findings can be justified by the contractual relationships based on trust already established between the partiesarties. Nevertheless, since 2011 this trend changed by an increase of the registered OTC. Thereafter, although the parties continued to trade bilaterally, these transactions were registered in a central counterparty in order to eliminate the inherent risks related to the OTC derivatives transactions. This change in the negotiation pattern may also be influenced by the mandatory reporting of transactions imposed by EMIR, that requires for some classes of derivatives the centralized clearing and for all other requires the implementation of risk mitigation techniques.