On the Cytotoxicity of Chiral Ruthenium Complexes Containing Sulfur Amino Acids against Breast Tumor Cells (MDA-231 and MCF-7)

Author(s):

Celisnolia M. Leite*, João Honorato de Araujo-Neto, Rodrigo S. Corrêa, Legna Colina-Vegas, Diego Martínez-Otero, Paulo R. Martins, Cristiane G. Silva and Alzir A. Batista*   Pages 1172 - 1182 ( 11 )

Abstract:

<P>Background: Breast cancer is one of the most common types among women. Its incidence progressively increases with age, especially after age 50. Platinum compounds are not efficient in the treatment of breast cancer, highlighting the use of other metals for the development of new chemotherapeutic agents. </P><P> Objective: This paper aims to obtain three new ruthenium compounds that incorporate sulfur amino acids in their structures and to investigate their cytotoxic activity in breast tumor cell lines. </P><P> Methods: Complexes with general formula [Ru(AA)(dppb)(bipy)] (complexes 1 and 2) or [Ru(AA)(dppb) (bipy)]PF6 (complex 3), where AA = L-cysteinate (1), D-penicillaminate (2), and L-deoxyalliinate (3), dppb = 1,4-bis(diphenylphosphino)butane and 2,2´-bipyridine, were obtained from the cis-[RuCl₂(dppb)(bipy)] precursor. The cytotoxicity of the complexes on MDA-MB-231 (triple negative human breast cancer); MCF-7 (double positive human breast cancer) and V79 (hamster lung fibroblast) was performed by the MTT (4,5- dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) method. The control agent was the cisplatin, which is a commercially available drug for cancer treatment. </P><P> Results: In complexes (1) and (2), the ligands are coordinated to the metal center by nitrogen and sulfur atoms, while in complex (3), coordination is through the oxygen and nitrogen atoms. These suggestions are based on the infrared and 31P{1H} NMR data. For complexes (1) and (2), their X-ray structures were determined confirming this suggestion. The three complexes are stable in a mixture of DMSO (80%) and biological medium (20%) for at least 48h and presented cytotoxicity against the MDA-MB-231 and MCF-7 tumor cells with reasonable selectivity indexes. </P><P> Conclusion: Our work demonstrated that ruthenium complexes containing sulfur amino acids, bipyridines and bisphosphines showed cytotoxicity against the MDA-MB-231 and MCF-7 cancer cell lines, in vitro, and that they interact weakly with the DNA (Deoxyribonucleic Acid) and the HSA (Human Serum Albumin) biomolecules.</P>

Keywords:

Ru(II)/amino acid complexes, diastereoisomers, breast cancer cells (MDA-MB-231 and MCF-7), cytotoxicity, DNA and HSA interaction, DNA docking.

Affiliation:

Departamento de Quimica, Universidade Federal de Sao Carlos-UFSCar, Sao Carlos, SP, Departamento de Quimica, Universidade Federal de Sao Carlos-UFSCar, Sao Carlos, SP, Departamento de Quimica, ICEB, Universidade Federal de Ouro Preto - UFOP, Ouro Preto, MG, Instituto de Quimica, Universidade Federal do Rio Grande do Sul-UFRGS, Porto Alegre, RS, Centro Conjunto de Investigacion en Quimica Sustentable, Universidad Nacional Autonoma de Mexico-UNAM, Toluca, Estado de Mexico, Instituto de Quimica, Universidade Federal de Goias-UFG, Goiania, GO, Instituto de Quimica, Universidade Federal de Goias-UFG, Goiania, GO, Instituto de Quimica, Universidade Federal de Goias-UFG, Goiania, GO

Graphical Abstract:

Read Full-Text article