Scavenging capacity and cytotoxicity of new Ru(II)-diphosphine/α-amino acid complexes

Author(s)

Velozo-Sa, Vivianne S. ; Oliveira, Regina M. M. ; Leite, Celisnolia M. ; Cominetti, Marcia R. ; Barbosa, Isabely M. M. ; Silva, Fabricio L. S. ; Feitosa, Natalia Martins ; Schultz, Mario S. ; Batista, Alzir A.

• Document type: Journal article
• Source: Polyhedron; v. 201, p. 13-pg., 2021-04-05.

Abstract

Reaction of a-amino acids (HL) with the precursor cis-[RuCl2(dppe)(2)] [HL = tyrosine (Tyr) or serine (Ser); dppe = 1,2-bis(diphenylphosphino)ethane] afforded the complexes [Ru(L-)(dppe)(2)]Cl {[Ru(Tyr-)(dppe)(2)] Cl (1) and [Ru(Ser-)(dppe)(2)]Cl (2)}. The new ruthenium complexes, with formulae [Ru(Tyr-)(dppe)(2)]Cl (1) and [Ru(Ser-)(dppe)(2)]Cl (2) were synthesized and characterized on the basis of elemental analysis, molar conductivity, IR/UV-Vis and P-31{H-1} NMR spectra. The in vitro cytotoxicities of the complexes against the MDA-MB-231 (breast adenocarcinoma) cell line were determined by the MTT assay. Complexes (1) and (2) show good cytotoxicity profiles against the MDA-MB-231 cell line with IC50 values of 2.05 +/- 0.71 mu M and 5.64 +/- 0.72 mu M, respectively, which are in the same order of values obtained for the metallodrug cisplatin (2.44 +/- 0.20 mu M) in the same assay. The selectivity indexes were significant for both complexes, showing lower cytotoxicity activity against the non-tumor breast cell line MCF-10A, with SI of 5.0 and 3.2, respectively. In addition, the lipophilicities of these complexes were determined and their interactions with human serum albumin (HSA) protein were investigated by fluorescence. The lipophilicities of the complexes suggest that this property has a significant effect on their cytotoxicity and the interaction measurements of the complexes with HSA indicate that the static fluorescence quenching mechanism is the main one involved in the formation of (1)-HSA and (2)-HSA adducts. Moreover, Van der Waals interactions and hydrogen bonds in (1)-HSA and electrostatic interaction in (2)-HSA are the predominant intermolecular forces between the complexes and the biomolecule. Furthermore, the antioxidant activity of the complexes was determined using the superoxide radical scavenging method, in vitro. Complex (1) was found to present a higher antioxidative activity, showing to be better than the standard antioxidant, vitamin C. In vivo toxicity assessment on zebrafish embryos showed that although the higher concentration of complex (1) has caused lethality of embryos, the effects of the concentration equivalent to the IC50 of complex (1) and cisplatin were similar in the hatching rate, mortality rate and morphological changes, showing a potential of complex (1) as a new anticancer agent. (C) 2021 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 12/13042-0 - Study of the expression of apoptotic genes, cell cycle, DNA repair and oxidative stress in cells of human lung carcinoma treated with complexes of formula [Ru(AA)(dppb) (4,4´-dimetylbipyridine)]PF6
• Grantee: Regina Maria Mendes Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/19342-2 - Metal complexes with dirivative ligands of lawsone and acylthioureas, with anticancer potential activities: study in vitro and in vivo.
• Grantee: Alzir Azevedo Batista
• Support Opportunities: Regular Research Grants