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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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.
Total Authors: 11
Document type: Journal article
Source: BIOMETALS; v. 30, n. 3, p. 321-334, JUN 2017.
Web of Science Citations: 10

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)

FAPESP's process: 12/22364-1 - Evaluation of mutagenic activity of Ruthenium (II) heteroleptic complexe with anti- Mycobacterium tuberculosis activity
Grantee:Rone Aparecido de Grandis
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/20078-4 - Effects of ruthenium compounds on the topoisomerase i enzyme as antitumoral mechanism
Grantee:Mariana Santoro de Camargo
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor