Cytotoxic activity and structural features of Ru(II)/phosphine/amino acid complexes

Author(s)

dos Santos, Edjane R. ^[1] ; Graminha, Angelica E. ^[1] ; Schultz, Mario S. ^[2] ; Correia, Isabel ^[3] ; Selistre-de-Araujo, Heloisa S. ^[4] ; Correa, Rodrigo S. ^[5] ; Ellena, Javier ^[6] ; Lacerda, Elisangela de Paula S. ^[7] ; Pessoa, Joao Costa ^[3] ; Batista, Alzir A. ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Quim, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Fed Rio de Janeiro, Nucleo Ecol & Desenvolvimento Socio Ambiental Mac, Campus Macae, BR-27910970 Macae, RJ - Brazil

^[3] Univ Lisbon, Inst Super Tecn, Ctr Quim Estrut, Av Rovisco Pais, P-1049001 Lisbon - Portugal

^[4] Univ Fed Sao Carlos, Dept Ciencias Fisiol, CP 676, BR-13565905 Sao Carlos, SP - Brazil

^[5] Univ Fed Ouro Preto, Campos Morro Cruzeiro, BR-35400000 Ouro Preto, MG - Brazil

^[6] Univ Sao Paulo, Inst Fis Sao Carlos, Dept Fis & Informat, Caixa Postal 369, BR-13560970 Sao Carlos, SP - Brazil

^[7] Univ Fed Goias, Inst Ciencias Biol, Lab Genet Mol & Citogenet, Goiania, Go - Brazil

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 182, p. 48-60, MAY 2018.
• Web of Science Citations: 6

Abstract

Thirteen new ruthenium amino acid complexes were synthesized and characterized. They were obtained by the reaction of alpha-amino acids (AA) with {[}RuCl2(P-P)(N-N)], where P-P = 1,4-bis(diphenylphosphino)butane (dppb) or 1,3-bis(diphenylphosphino)propane (dppp) and N-N = 4,4'-dimethyl-2,2'-bipyridine (4'-Mebipy), 5,5'-dimethyl-2,2'-bipyridine (5'-Mebipy) or 4,4'-Methoxy-2-2'-bipyridine (4'-MeObipy). This afforded a family of complexes formulated as {[}Ru(AA-H)(P-P)(N-N)]PF6, where AA = glycine (Gly), L-alanine (Ala), L-valine (Val), L-tyrosine (Tyr), L-tryptophan (Trp), L-histidine (His) and L-methionine (Met). All compounds were characterized by elemental analysis, spectroscopic and electrochemical techniques. The {[}Ru(AA-H)(P-P)(N-N)]PF6 complexes are octahedral (the AA-H ligand binding involves N-amine and O-carboxylate), diamagnetic (low-spin d(6), S = 0) and present bands due to electronic transitions in the visible region. H-1, C-13[H-1] and P-31[H-1] NMR spectra of the complexes indicate the presence of C-2 symmetry, and the identification of diastereoisomers. In vitro cytotoxicity assays of the compounds and cisplatin were carried out using MDA-MB-231 (human breast) tumor cell line and a non-tumor breast cell line (MCF-10A). Most complexes present promising results with IC50 values comparable with the reference drug cisplatin and high selectivity indexes were found for the complexes containing L-Trp. The binding of two Ru-precursors of the type {[}RuCl2(dppb)(N N)] (N-N = 4'-meObipy or 4'-Mebipy) to the blood transporter protein human serum albumin (HSA) was evaluated by fluorescence and circular dichroism spectroscopy. Both complexes bind HSA, probably in the hydrophobic pocket near Trp214, and the Ru-complex containing 4'-MeObipy shows higher affinity for HSA than the 4'-Mebipy one. (AU)

• FAPESP's process: 12/06013-4 - Study of apoptosis gene expression, celular cyclic, DNA repair and oxidative stress in cells of human lang carcinoma treated with complexes with general formula [Ru(AA)(dppb)(bipy)]PF6
• Grantee: Alzir Azevedo Batista
• Support Opportunities: Regular Research Grants