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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Human topoisomerase inhibition and DNA/BSA binding of Ru(II)-SCAR complexes as potential anticancer candidates for oral application

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Autor(es):
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De Grandis, Rone A. ; de Camargo, Mariana S. ; da Silva, Monize M. ; Lopes, Erica O. ; Padilha, Elias C. ; Resende, Flavia A. ; Peccinini, Rosangela G. ; Pavan, Fernando R. ; Desideri, Alessandro ; Batista, Alzir A. ; Varanda, Eliana A.
Número total de Autores: 11
Tipo de documento: Artigo Científico
Fonte: BIOMETALS; v. 30, n. 3, p. 321-334, JUN 2017.
Citações Web of Science: 8
Resumo

Three ruthenium(II) phosphine/diimine/picolinate complexes were selected aimed at investigating anticancer activity against several cancer cell lines and the capacity of inhibiting the supercoiled DNA relaxation mediated by human topoisomerase IB (Top 1). The structure-lipophilicity relationship in membrane permeability using the Caco-2 cells have also been evaluated in this study. SCAR 5 was found to present 45 times more cytotoxicity against breast cancer cell when compared to cisplatin. SCAR 4 and 5 were both found to be capable of inhibiting the supercoiled DNA relaxation mediated by Top 1. Interaction studies showed that SCAR 4 and 5 can bind to DNA through electrostatic interactions while SCAR 6 is able to bind covalently to DNA. The complexes SCAR were found to interact differently with bovine serum albumin (BSA) suggesting hydrophobic interactions with albumin. The permeability of all complexes was seen to be dependent on their lipophilicity. SCAR 4 and 5 exhibited high membrane permeability (P-app > 10 x 10(-6) cm.s(-1)) in the presence of BSA. The complexes may pass through Caco-2 monolayer via passive diffusion mechanism and our results suggest that lipophilicity and interaction with BSA may influence the complexes permeation. In conclusion, we demonstrated that complexes have powerful pharmacological activity, with different results for each complex depending on the combination of their ligands. (AU)

Processo FAPESP: 12/22364-1 - Avaliação da atividade mutagênica de complexo heteroléptico de rutênio(II) com atividade anti-Mycobacterium tuberculosis
Beneficiário:Rone Aparecido de Grandis
Linha de fomento: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 13/20078-4 - Efeitos de compostos de rutênio sobre a enzima topoisomerase i como mecanismo antitumoral
Beneficiário:Mariana Santoro de Camargo
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado