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Molecular docking studies of the interaction between propargylic enol ethers and human DNA topoisomerase IIα

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Detalhes bibliográficos
Resumo:Having identified a novel human DNA topoisomerase IIa (TOP2) catalytic inhibitor from a small and structure-focused library of propargylic enol ethers, we decided to analyze if the chirality of these compounds plays a determinant role in their antiproliferative activity. In this study, we describe for the first time the synthesis of the corresponding enantiomers and the biological evaluation against a panel of representative human solid tumor cell lines. Experimental results show that chirality does not influence the reported antiproliferative activity of these compounds. Docking studies of corresponding enantiomers against TOP2 reinforce the finding that the biological effect is not chiral-dependent and that these family of compounds seem to act as TOP2 catalytic inhibitors.
Autores principais:Silveira-Dorta, Gastón
Outros Autores:Sousa, Inês J.; Ríos-Luci, Carla; Martín, Víctor S.; Fernandes, Miguel X.; Padrón, José M.
Assunto:Antitumor agents Chirality Docking studies Enzyme inhibitors Topoisomerase IIa . Faculdade de Ciências Exatas e da Engenharia
Ano:2013
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade da Madeira
Idioma:inglês
Origem:DigitUMa - Repositório da Universidade da Madeira
Descrição
Resumo:Having identified a novel human DNA topoisomerase IIa (TOP2) catalytic inhibitor from a small and structure-focused library of propargylic enol ethers, we decided to analyze if the chirality of these compounds plays a determinant role in their antiproliferative activity. In this study, we describe for the first time the synthesis of the corresponding enantiomers and the biological evaluation against a panel of representative human solid tumor cell lines. Experimental results show that chirality does not influence the reported antiproliferative activity of these compounds. Docking studies of corresponding enantiomers against TOP2 reinforce the finding that the biological effect is not chiral-dependent and that these family of compounds seem to act as TOP2 catalytic inhibitors.

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