Ru(II)-based complexes with N-(acyl)-N ',N '-(disubstituted)thiourea ligands: Synthesis, characterization, BSA- and DNA-binding studies of new cytotoxic agents against lung and prostate tumour cells

Author(s)

Correa, Rodrigo S. ; de Oliveira, Katia M. ; Delolo, Fabio G. ; Alvarez, Anislay ; Mocelo, Raul ; Plutin, Ana M. ; Cominetti, Marcia R. ; Castellano, Eduardo E. ; Batista, Alzir A.

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 150, p. 9-pg., 2015-09-01.

Abstract

Four ruthenium(II)-based complexes with N-(acyl)-N',N'-(disubstituted)thiourea derivatives (Th) were obtained. The compounds, with the general formula trans-[Ru(PPh3)(2)(Th)(bipy)]PF6, interact with bovine serum albumin (BSA) and DNA. BSA-binding constants, which were in the range of 3.3-6.5 x 10(4) M-1, and the thermodynamic parameters (Delta G, Delta H and Delta S), suggest spontaneous interactions with this protein by electrostatic forces due to the positive charge of the complexes. Also, binding constant by spectrophotometric DNA titration (Kb = 0.8-1.8 x 10(4) M-1) and viscosity studies indicate weak interactions between the complexes and DNA. Cytotoxicity assays against DU-145 (prostate cancer) and A549 (lung cancer) tumour cells revealed that the complexes are more active in tumour cells than in normal (L929) cells, and that they present high cytotoxicity (low IC50 values) compared with the reference metallodrug, cisplatin. (C) 2015 Published by Elsevier Inc. (AU)

• FAPESP's process: 13/26559-4 - Structural modifications in biologically active Ru(II) complexes toward the design of new metallodrug candidates
• Grantee: Rodrigo de Souza Corrêa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/04147-9 - Evaluation of anticancer properties of ruthenium(II)complexes containing lapachol and lawsone bioligands
• Grantee: Katia Mara de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate