DNA binding, topoisomerase inhibition and cytotoxicity of palladium(II) complexes with 1,10-phenanthroline and thioureas

Autor(es)

Barra, Carolina V. ^{[1, 2]} ; Rocha, Fillipe V. ^[3] ; Morel, Laurent ^[4] ; Gautier, Arnaud ^[5] ; Garrido, Saulo S. ^[6] ; Mauro, Antonio E. ^[1] ; Frem, Regina C. G. ^[1] ; Netto, Adelino V. G. ^[1]

Afiliação do(s) autor(es)

^[1] UNESP, Inst Quim, Dept Quim Geral & Inorgan, BR-14801970 Araraquara, SP - Brazil

^[2] Inst Fed Educ Ciencia & Tecnol, BR-14801600 Araraquara, SP - Brazil

^[3] Univ Fed Sao Carlos, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[4] Univ Clermont Ferrand, Clermont Univ, GreD UMR CNRS 6247, INSERM U931, 24 Ave Landais, F-63177 Aubiere - France

^[5] Univ Clermont Ferrand, Clermont Univ, ICCF, CNRS, UMR 6296, F-63177 Aubiere - France

^[6] UNESP, Inst Quim, Dept Bioquim & Tecnol Quim, BR-14801970 Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Inorganica Chimica Acta; v. 446, p. 54-60, MAY 1 2016.
• Citações Web of Science: 18

Resumo

Metallointercalators represent a promising alternative in cancer chemotherapy. We present herein DNA binding, topoisomerase inhibition and cytotoxic studies on a series of complexes of general formulae {[}Pd (phen)(tu{*})(2)](2+) incorporating the intercalator 1,10-phenanthroline and thiourea ligands (L = thiourea 1, N-methylthiourea 2, N,N'-dimethylthiourea 3). DNA-unwinding results showed that the complexes can induce the unwinding of the plasmid DNA. The binding constants (K-b) for the interaction of the complexes with SS-DNA were determined by UV spectroscopy. Competitive experiments with ethidium bromide (EB) were investigated by fluorescence spectroscopy and show that all the complexes were able to displace EB from the DNA-EB complex. The results suggest that they may interact with DNA by intercalation. Compounds were tested against human oral carcinoma cell line (KB), human breast cancer cell line (MCF7) and cisplatin-resistant human breast cancer cell line (MCF7-R) and showed good cytotoxic activity towards MCF7-R. Compounds 2 and 3 were also able to cause topo II inhibition. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 14/11340-0 - NOVOS COMPLEXOS ORGANOMETÁLICOS DE Pd(II): INVESTIGAÇÃO DE SUAS POTENCIALIDADES COMO INIBIDORES DE CATEPSINA B
• Beneficiário: Carolina Valério Barra Rocha
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado