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Orientador(es)
Resumo(s)
Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N
Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with
different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling
products to the corresponding amino compounds. The aminodi(hetero)arylamines thus
obtained were evaluated for their growth inhibitory effect on four human tumor cell lines
MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung
cancer) and HepG2 (hepatocellular carcinoma). The toxicity to non-tumor cells was also
evaluated using a porcine liver primary cell culture (PLP1), established by us. The
aminodi(hetero)arylamine with the NH2 group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound
giving the lowest GI50 values (1.30–1.63 μM) in all the tested human tumor cell lines,
presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the
cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was
observed that it altered the cell cycle profile causing a decrease in the percentage of cells in
the G0/G1 phase and an increase of the apoptosis levels.
Descrição
Palavras-chave
Thieno[3,2-b]pyridines Aminodi(hetero)arylamines Buchwald-Hartwig C-N coupling Antitumoral activity Toxicity Cell cycle
Contexto Educativo
Citação
Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Peixoto, Daniela; Abreu, Rui M.V.; Vale-Silva, Luís A.; Pinto, Eugénia; Lima, Raquel T.; Alvelos, M. Inês; Vasconcelos, M. Helena; Queiroz, Maria-João R.P. (2012) – Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells. Molecules. ISSN 1420-3049. 17:4, p. 3834-3843
Editora
MDPI