ITQB: OC - MA Dissertations
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- Synthesis, characterization and antiproliferative activity of iridium organometallic complexes bearing N,N-chelating ligandsPublication . Meireles, Marta Sofia Horta; Lenis-Rojas, Oscar A.; Fernandes, Alexandra R."Platinum-based complexes are included in approximately 50–70 % of chemotherapeutic regimens. However, these drugs cause serious side effects in normal tissues, as well as resistance problems which are associated with therapy failure. Consequently, novel anticancer drugs with improved pharmacological properties are needed. Recently, iridium organometallic complexes have demonstrated good solubility in aqueous solutions, stability and alternative modes of action relative to the conventional chemotherapeutic drugs. This thesis reports the synthesis, characterization and in vitro antiproliferative potential of four iridium half-sandwich complexes [(η5-Cp*)Ir(N,N)Cl][Cl] (where Cp* = pentamethylcyclopentadienyl ligand; N,N = 1,10-phenanthroline-5,6-dione (L1), 6,7-dimethyl-2,3-bis(pyridin-2-yl)quinoxaline (L2), 2-[1-(p-tolyl)-1H-1,2,3-triazol-4-yl]pyridine (L3) or 1,1′-di-p-tolyl-1H,1′H-4,4′-bi(1,2,3-triazole) (L4) bidentate chelating ligands). All complexes were fully characterized by proton and carbon (1H and 13C) Nuclear Magnetic Resonance (NMR) spectroscopy, Electrospray Ionization High-Resolution Mass Spectrometry (ESI-HRMS) and Fourier-Transformed Infrared (FTIR) spectroscopy.(...)"
- Developing fluorescent antifungal azole compounds for live fungal cell imagingPublication . Ferreira, Luana André; Lima, Luís; Pimentel, Catarina"Invasive fungal infections are on the rise and pose a serious health threat due to the lack of effective antifungals and the recent emergence of resistant fungi. Therefore, there is an urgent need to develop new and improved antifungal agents. The main objective of this work was to design and synthesize new antifungal azole compounds by molecular simplification based on the commercial drug fluconazole, and to include a fluorophore moiety in the designed compounds for live cell imaging purposes. Eight target compounds were synthesized in three structural families based on a central tertiary amine substituted with azole, dihalogenobenzyl, and fluorophore functions. The target compounds were characterized by NMR, mass spectrometry, UV-Vis and fluorescence spectroscopy. The antifungal potential of the compounds against Candida glabrata, one of the most dangerous causative agents of invasive candidiasis, was tested in vitro and their effect on intracellular ergosterol levels was measured using HPLC. Lastly, the compounds containing pyrene and dansyl fluorophores were studied by live cell imaging.(...)"
- Exploring novel copper(II) binding azole compounds as potential antifungal drugsPublication . Pissarro, Teresa; Lima, Luís; Pimentel, Catarina"Invasive fungal infections are a major cause of morbidity and mortality among hospitalized patients and immunocompromised individuals. The increasing resistance of pathogenic fungi to the limited number of antifungal classes available makes the development of new and improved antifungals a pressing issue. This work aims to synthesize new azole compounds by molecular simplification of the model antifungal drug fluconazole while incorporating chemical functions that bind copper(II), to explore a potential synergy between the azoles and the metal. The target compounds designed are based on a central amine functionalized with three functions: an azole, a dihalogenobenzyl, and a varying copper(II) binding function. The 15 target compounds synthesized are organized in three families, which differ on the azole used (triazole or imidazole) and the length of the alkyl chain separating the central amine and the azole. Differences within each family are the copper(II) binding function used and, in one case, also the dihalogenobenzyl moiety. Such structural variations are expected to allow for a structure-activity relationship study based on the results of biological activity assays performed.(...)"