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Título: COPPER(II) COMPLEXES DERIVED FROM NACYLHYDRAZONIC LIGANDS AS AN ANTITUMOR ALTERNATIVE TO PLATINUM COMPOUNDS: SYNTHESIS, CHARACTERIZATION, STUDIES IN SOLUTION AND PHARMACOLOGICAL POTENTIAL
Autor: FAGNER DA SILVA MOURA
Colaborador(es): NICOLAS ADRIAN REY - Orientador
Catalogação: 13/JAN/2025 Língua(s): ENGLISH - UNITED STATES
Tipo: TEXT Subtipo: THESIS
Notas: [pt] Todos os dados constantes dos documentos são de inteira responsabilidade de seus autores. Os dados utilizados nas descrições dos documentos estão em conformidade com os sistemas da administração da PUC-Rio.
[en] All data contained in the documents are the sole responsibility of the authors. The data used in the descriptions of the documents are in conformity with the systems of the administration of PUC-Rio.
Referência(s): [pt] https://www.maxwell.vrac.puc-rio.br/projetosEspeciais/ETDs/consultas/conteudo.php?strSecao=resultado&nrSeq=69117&idi=1
[en] https://www.maxwell.vrac.puc-rio.br/projetosEspeciais/ETDs/consultas/conteudo.php?strSecao=resultado&nrSeq=69117&idi=2
DOI: https://doi.org/10.17771/PUCRio.acad.69117
Resumo:
Cancer can be considered a collection of various diseases that collectively lead to an imbalance in the tissues from which they originate. The genesis of tumors is generally associated with mutations that accumulate within cells. The altered cell acquires an increased capacity of proliferation, undergoing clonal expansion and transmitting its genes to daughter cells. Disordered proliferation can form a solid and intricate mass of altered cells within the organ where the tumor originated. Current cancer treatments focus on diagnosing the type of cell, its location and severity, guidance, selecting the best treatment options, and monitoring the progress. In the latter half of the 1960s, Rosenberg discovered the antitumor activity of cisplatin, which spurred the search for new metal-based anticancer agents. Despite this, few inorganic anticancer drugs have shown auspicious due to toxicity issues. In this context, N-acylhydrazones and their copper(II) complexes have been suggested as promising compounds for achieving this objective. Copper(II) complexes have been presented in the literature as an alternative to platinum-based anticancer compounds, given that copper is an essential trace element with fewer side effects. In recent decades, many copper(II) coordination compounds exhibiting antitumor activity have been reported as promising active compounds against tumor cells, with some advancing to clinical trials, such as Casiopeínas (trademark), which interact with cells in various ways. Our research group has experience with copper(II) complexes exhibiting reported antitumor activity. Additionally, N,O-donor N-acylhydrazone ligands, both free and coordinated, have demonstrated biological activity as anticancer agents. This has motivated the design of a new generation of similar ligands to enhance antitumor activity. This work encompasses the synthesis, acquisition, and complete characterization of novel N-acylhydrazone ligands, which were thoroughly characterized, as well as their new copper(II) complexes obtained from three different starting salts. The study includes the reactivity, spectroscopic, electrochemical, and antiproliferative properties of a new generation of mono- and binuclear copper(II) complexes derived from these N-acylhydrazone ligands. Of the ten synthesized complexes, six showed reactivity towards human serum albumin (HSA), and three complexes derived from the ligand containing furan as a substituent had their antiproliferative activity evaluated, exhibiting greater activity than cisplatin.
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