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

Resumo
Thirteen new ruthenium amino acid complexes were synthesized and characterized. They were obtained by the reaction of α-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 d6, S = 0) and present bands due to electronic transitions in the visible region. 1H, 13C{1H} and 31P{1H} NMR spectra of the complexes indicate the presence of C2 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)(NN)] (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.
Descrição
Palavras-chave
Ruthenium complexes, Human serum albumin, Circular dichroism
Citação
SANTOS, E. R. dos et al. Cytotoxic activity and structural features of Ru(II)/phosphine/amino acid complexes. Journal of Inorganic Biochemistry, v. 182, p. 48-60, mai. 2018. Disponível em: <https://www.sciencedirect.com/science/article/pii/S016201341730510X>. Acesso em: 05 abr. 2018.