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Bioorg Chem ; 77: 269-279, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29421702

RESUMO

Four new metal complexes were synthesized and screened for their cytotoxic activity after sufficient assertion from the preliminary DNA binding studies. The metal complexes could bind to CT-DNA through intercalation binding mode. This has also been confirmed by the molecular docking studies. The DNA cleavage efficiencies of these complexes with pBR322 DNA were investigated by gel electrophoresis. The complexes were found to promote the cleavage of pBR322 DNA from the supercoiled form I to the open circular form II in the presence of an oxidizing agent (H2O2). The in vitro chemosensitivity of the studied complexes exhibits significant cytotoxic effects, compared to those reported for cisplatin. These findings represent a prompting to search for the probable interaction of these complexes with other cellular elements of fundamental consequence in cell proliferation. The in vitro anticancer activities indicate that the Cu(II) complex is active against the selected human tumor cell lines, and the order of in vitro anticancer activities is consistent with the DNA-binding affinities. Towards noncancerous cell line, Cu(II) complex exhibits very low toxicity. On the other hand all the complexes have been found to exhibit cytotoxic effects against cancerous cell lines with potency more than that of the widely used drug cisplatin and hence they have the potential to act as promising anticancer agents. Captivatingly, they are non-toxic to normal cell lymphocytes revealing that they are selective in killing only the cancer cells.


Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Sondas de DNA/farmacologia , DNA/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Histidina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzimidazóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sondas de DNA/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Técnicas Eletroquímicas , Histidina/química , Humanos , Ligantes , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-Atividade
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