Cytotoxic activity and structural features of Ru(II)/phosphine/amino acid complexes.
SANTOS, Edjane R.; GRAMINHA, Angelica E.; SCHULTZ, Mario S.; CORREIA, Isabel; SELISTRE-DE-ARAÚJO, Heloisa S.; CORRÊA, Rodrigo S.; ELLENA, Javier; LACERDA, Elisângela de Paula S.; PESSOA, João Costa; BATISTA, Alzir A.
SANTOS, Edjane R.; GRAMINHA, Angelica E.; SCHULTZ, Mario S.; CORREIA, Isabel; SELISTRE-DE-ARAÚJO, Heloisa S.; CORRÊA, Rodrigo S.; ELLENA, Javier; LACERDA, Elisângela de Paula S.; PESSOA, João Costa; BATISTA, Alzir A.
 Abstract: Thirteen new ruthenium amino acid complexes were synthesized and characterized. They were obtained by the reaction of a-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)(NeN)] (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. | |
| Journal of Inorganic Biochemistry |
| v. 182, p. 48-60 - Ano: 2018 |
| Fator de Impacto: 3,348 |
| http://dx.doi.org/10.1016/j.jinorgbio.2017.12.010 |  @article={002874803,author = {SANTOS, Edjane R.; GRAMINHA, Angelica E.; SCHULTZ, Mario S.; CORREIA, Isabel; SELISTRE-DE-ARAÚJO, Heloisa S.; CORRÊA, Rodrigo S.; ELLENA, Javier; LACERDA, Elisângela de Paula S.; PESSOA, João Costa; BATISTA, Alzir A.},title={Cytotoxic activity and structural features of Ru(II)/phosphine/amino acid complexes},journal={Journal of Inorganic Biochemistry},note={v. 182, p. 48-60},year={2018}} |
