COMPLEXOS METÁLICOS DE 2-PIRIDINOFORMAMIDA TIOSSEMICARBAZONAS: ESTUDOS EM SOLUÇÃO, NO ESTADO SÓLIDO E ATIVIDADE CITOTÓXICA / METAL COMPLEXES OF 2-PYRIDINEFORMAMIDE THIOSEMICARBAZONES: SOLUTION STUDIES, SOLID STATE STUDIES AND CYTOTOXIC ACTIVITY.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

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.

ASSUNTO(S)

iron complexes complexos de ferro 2-pyridineformamide thiosemicarbazones constantes de estabilidade 2-piridinoformamida tiossemicarbazonas stability constants

ACESSO AO ARTIGO

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