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1.
Future Med Chem ; 6(16): 1791-810, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25574531

RESUMO

Metabolic processes are altered in cancer cells, which obtain advantages from this metabolic reprogramming in terms of energy production and synthesis of biomolecules that sustain their uncontrolled proliferation. Due to the conceptual progresses in the last decade, metabolic reprogramming was recently included as one of the new hallmarks of cancer. The advent of high-throughput technologies to amass an abundance of omic data, together with the development of new computational methods that allow the integration and analysis of omic data by using genome-scale reconstructions of human metabolism, have increased and accelerated the discovery and development of anticancer drugs and tumor-specific metabolic biomarkers. Here we review and discuss the latest advances in the context of metabolic reprogramming and the future in cancer research.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Biologia Computacional , Ensaios de Triagem em Larga Escala , Humanos , Neoplasias/patologia
2.
Eur J Med Chem ; 84: 530-6, 2014 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-25063943

RESUMO

Twelve cyclometallated palladium(II) complexes containing primary aromatic amines [benzylamine (a), (R)-1-(1-naphthyl)ethylamine (b) and 2-phenylaniline (c)] as anionic bidentate (C,N)(-) ligands have been evaluated against a panel of human adenocarcinoma cell lines (A549 lung, MDA-MB231 and MCF7 breast, and the cisplatin resistant HCT116 colon). The results revealed a remarkable antiproliferative activity of the triphenylphosphane mononuclear compounds 3-4 (series a, b, c) and the best inhibition was provided for 3c and 4c with the 2-phenylaniline ligand and a six membered chelate ring. Interestingly, 3c and 4c were 14 and 19 times more potent than cisplatin for the inhibition of the cisplatin resistant HCT116 human adenocarcinoma cell line, respectively. Cyclopalladated complexes 3c and 4c exercise their antiproliferative activity over A549 cells mainly through the induction of apoptosis (38 and 31-fold increase in early apoptotic cells, respectively).


Assuntos
Aminas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aminas/síntese química , Aminas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
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