Ru(II)/bisphosphine/diimine/amino acid complexes: diastereoisomerism, cytotoxicity, and inhibition of tumor cell adhesion to collagen type I

Abstract

We herein report the synthesis and characterization of Ru(II)/amino acid complexes with general formula [Ru(AA-H)(dppb)(4-mebipy)](PF₆), where AA-H means the deprotonated amino acids Gly, Ala, Val, Met, Trp, Tyr, and Ser; dppb is 1,4-bis(diphenylphosphino)butane and 4-mebipy = 4,4′-dimethyl-2,2′-bipyridine. The complexes were characterized by ³¹P{¹H}, ¹³C, and ¹H NMR spectroscopy, as well as X-ray crystallographic analysis of [Ru(DL-Ala-H)(dppb)(4-mebipy)]⁺, suggesting the presence of diastereoisomers. The complexes exhibit IC₅₀ values against breast tumor cells (MDA-MB-231) comparable with cisplatin. In addition, the Ru(II)-based complex with tryptophan inhibited tumor cell adhesion to collagen type I. Therefore, the use of ruthenium complexes containing amino acids can be an interesting tool for development of new therapeutic agents.

Keywords:

• Ruthenium complexes
• amino acids
• diastereoisomer
• cytotoxicity
• collagen adhesion

Acknowledgements

We would like to thank CNPq, CAPES, FAPEMIG, and FAPESP (12/06013-4) for the financial support. R.S. Correa would like to thank FAPESP for the postdoctoral fellowship (Grant number 13/26559-4).