$$\newcommand{\bra}[1]{\left<#1\right|}\newcommand{\ket}[1]{\left|#1\right>}\newcommand{\bk}[2]{\left<#1\middle|#2\right>}\newcommand{\bke}[3]{\left<#1\middle|#2\middle|#3\right>}$$
X
INFORMAÇÕES SOBRE DIREITOS AUTORAIS


As obras disponibilizadas nesta Biblioteca Digital foram publicadas sob expressa autorização dos respectivos autores, em conformidade com a Lei 9610/98.

A consulta aos textos, permitida por seus respectivos autores, é livre, bem como a impressão de trechos ou de um exemplar completo exclusivamente para uso próprio. Não são permitidas a impressão e a reprodução de obras completas com qualquer outra finalidade que não o uso próprio de quem imprime.

A reprodução de pequenos trechos, na forma de citações em trabalhos de terceiros que não o próprio autor do texto consultado,é permitida, na medida justificada para a compreeensão da citação e mediante a informação, junto à citação, do nome do autor do texto original, bem como da fonte da pesquisa.

A violação de direitos autorais é passível de sanções civis e penais.
Coleção Digital

Avançada


Estatísticas | Formato DC |



Título: NEW PLATINUM(II) AND COPPER(II) COMPLEXES DERIVED FROM 1,2,3-TRIAZOLIC OXIMES AS POTENTIAL ANTITUMOR AGENTS AND PROTOTYPES OF BIOREDUCTIVE PRODRUGS
Autor: SUMAIA HOTTES
Instituição: PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO - PUC-RIO
Colaborador(es):  NICOLAS ADRIAN REY - ADVISOR
Nº do Conteudo: 24950
Catalogação:  21/07/2015 Idioma(s):  PORTUGUESE - BRAZIL
Tipo:  TEXT Subtipo:  THESIS
Natureza:  SCHOLARLY PUBLICATION
Nota:  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.
Referência [pt]:  https://www.maxwell.vrac.puc-rio.br/colecao.php?strSecao=resultado&nrSeq=24950@1
Referência [en]:  https://www.maxwell.vrac.puc-rio.br/colecao.php?strSecao=resultado&nrSeq=24950@2
Referência DOI:  https://doi.org/10.17771/PUCRio.acad.24950

Resumo:
Cancer pathology is of great importance, since it is the second leading cause of death worldwide, with a prospect of growth in the number of cases for the next decades. Current chemotherapy treatments are characterized by high cost and a relatively low therapeutic index and are associated with several side effects and tumor resistance. Therefore, many efforts have been focused on the search for new drugs with an improved pharmacological profile and tumor-resistant lineage activity, as well as the feasibility of new administration routes. In this regard, different approaches have been employed for the design of metal-based anticancer drugs, such as the development of new cisplatin analogue complexes, as well as complexes that may be more selective to the tumor environment. A very promising strategy involves the preparation of high oxidation state inert metal complexes, which may act as prodrugs, reaching the tumor target without prior reduction or significant transformations. Only inside the tumor mass, due to hypoxia conditions (low oxygen) not normally found in normal tissues, these compounds would be reduced, originating the active species which would then attack the target more easily. Copper, by presenting two oxidation states whose reduction potential is accessible within the range of the cellular redox potential, is a promising element. In this context, two copper(II) complexes and two platinum(II) complexes with the isomeric ligands 1- and 2-phenyl-1,2,3-triazole-4-carboxaldehyde oxime were synthesized in the present study, which have never before been explored in the context of Coordination Chemistry, with only the copper complexes, in theory, demonstrating the potential to act as bioreductive prodrugs. The complexes were characterized by elemental analysis (CHN and AAS), vibrational spectroscopy and thermogravimetry. EPR studies in solid state were performed for the copper(II) complexes, while the platinum(II) complexes were also characterized by 195Pt NMR. Computer modeling was used as a complementary resource for structural propositions and assignment of the vibrational bands of the complexes, with the exception of coordination compound [Cu2(mu-L1)2(HL1)(ClO4)2(OH2)]·2H2O (1), whose structure was determined by single crystal X-ray diffraction. The other mononuclear copper(II) complex is cis-[Cu(HL2)2Cl2] (2). On the other hand, the platinum(II) compounds are mononuclear and as expected, quadratic, according to the formulae cis-[Pt(HL1)2Cl2]1 H2O (3) and cis-[Pt(HL2)2Cl2] (4). The copper complexes were tested against the leukemic cell lines U937 and THP-1, with complex 1 and HL1 also being tested on normal PBMC blood cells. Both complexes reduced cell viability in a concentration-dependent manner in the tested tumor lines; The activity profile towards U937 cells was similar for 1 and 2. However, compound 1 was twice as active as 2 against cell line THP-1. It is worth noting that 1 was 23 percent more toxic against the leukemic cell line THP-1 when compared to normal PBMC cells. The platinum complexes, alternatively, were tested against the K562 cell line, chronic myeloid leukemia, and both demonstrated similar toxicity, approximately 5x higher than carboplatin.

Descrição Arquivo
COVER, ACKNOWLEDGEMENTS, RESUMO, ABSTRACT, SUMMARY AND LISTS  PDF
CHAPTER 1  PDF
CHAPTER 2  PDF
CHAPTER 3  PDF
CHAPTER 4  PDF
CHAPTER 5  PDF
CHAPTER 6  PDF
CHAPTER 7  PDF
REFERENCES AND APPENDICES  PDF
Logo maxwell Agora você pode usar seu login do SAU no Maxwell!!
Fechar Janela



* Esqueceu a senha:
Senha SAU, clique aqui
Senha Maxwell, clique aqui