ETDs @PUC-Rio
| Título: | METAL COMPLEXES OF 2-PYRIDINEFORMAMIDE THIOSEMICARBAZONES: SOLUTION STUDIES, SOLID STATE STUDIES AND CYTOTOXIC ACTIVITY. | ||||||||||||||||||||||||||||||||||||||||
| Autor: |
FELIPE DE SOUZA DIAS DOS SANTOS VILHENA |
||||||||||||||||||||||||||||||||||||||||
| Colaborador(es): |
LETICIA REGINA DE SOUZA TEIXEIRA - Orientador |
||||||||||||||||||||||||||||||||||||||||
| Catalogação: | 23/JUL/2008 | Língua(s): | PORTUGUESE - BRAZIL |
||||||||||||||||||||||||||||||||||||||
| 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=11957&idi=1 [en] https://www.maxwell.vrac.puc-rio.br/projetosEspeciais/ETDs/consultas/conteudo.php?strSecao=resultado&nrSeq=11957&idi=2 |
||||||||||||||||||||||||||||||||||||||||
| DOI: | https://doi.org/10.17771/PUCRio.acad.11957 | ||||||||||||||||||||||||||||||||||||||||
| Resumo: | |||||||||||||||||||||||||||||||||||||||||
|
Thiosemicarbazones and their metal complexes present a wide
range of
bioactivities. It has been shown that the antitumoral
action of á(N)-heterocyclic
thiosemicarbazones occurs through the inhibition of
ribonucleotide diphosphate
reductase (RDR), a key enzyme involved in the conversion of
ribonucleotides into
deoxyribonucleotides during DNA syntheses. The active form
of the drugs are
their iron complexes. Hence the preparation of new iron
complexes with á(N)-
heterocyclic thiosemicarbazones constitutes an interesting
strategy in designing
antitumoral drug candidates. In the present work the
interactions of 2-
pyridineformamide thiosemicarbazone (H2Am4DH) and its N(4)-
methyl
(H2Am4Me), N(4)-ethyl (H2Am4Et) and N(4)-phenyl (H2Am4Ph)
derivatives
with Cu(II) as well as Fe(III) ions in aqueous solution
were studied, monitored in
the visible region by the variations of the absorption
spectrum. The cumulative
protonation constants â HL and â H2L+ were determined for
the ligands by a
potentiometric method and were used in the calculation of
the complex formation
constants. The iron(III) complexes [Fe(2Am4DH)2]Cl, [Fe
(2Am4Me)2]Cl,
[Fe(2Am4Et)2]Cl and [Fe(2Am4Ph)Cl3] were obtained and
characterized. The
values of magnetic moments in the 1.59-1.66 BM range are
close to the calculated
value of 1.73 BM, characteristic of the presence of one
unpaired electron as in low
spin iron(III) complexes. The infrared data for the
complexes indicate
coordination of the thiosemicarbazones through the Npy-N-S
chelating system.
The resemblance of electrochemical behaviors suggests that
the structures of the
complexes in solution are also very similar. The toxicity
of the
thiosemicarbazones and their metal complexes against
Artemia salina was assayed
as a prescreening of antitumoral action. The low values of
LD50 obtained for the
studied compounds in this assay indicate that they could
present antineoplastic
properties. Moreover, the determined values of FeIII/FeII
redox potentials for the complexes fall in the range of
cellular reductants. Therefore, if the complexes
present antitumoral activity, their biochemical pathway
could involve FeIII/FeII
reduction by cellular thiols, as suggested previously for
iron complexes of other
thiosemicarbazones.
|
|||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||