Ru(II)/N-N/PPh3 complexes as potential anticancer agents against MDA-MB-231 cancer cells (N-N = diimine or diamine)

Author(s)

Ribeiro, Gabriel H. ^[1] ; Colina-Vegas, Legna ^[1] ; Clavijo, Juan C. T. ^[2] ; Ellena, Javier ^[2] ; Cominetti, Marcia R. ^[3] ; Batista, Alzir A. ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Quim, Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil

^[3] Univ Fed Sao Carlos, Dept Gerontol, Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 193, p. 70-83, APR 2019.
• Web of Science Citations: 1

Abstract

The rational design of anticancer agents that acts in specific biological targets is one of the most effective strategies for developing chemotherapeutic agents. Aiming at obtaining new ruthenium (II) compounds with good cytotoxicity against tumor cells, a series of new complexes of general formula {[}RuCl(PPh3)(Hdpa)(N-N)]Cl {[}PPh3 = triphenylphosphine, N-N = 2,2'-dipyridylamine (Hdpa) (1), 1,2-diaminoethane (en) (2), 2,2'-bipyridine (bipy) (3), 5,5'-dimethyl-2,2'-bipyridine (dmbipy) (4), 1,10-phenanthroline (phen) (5) and 4,7-diphenyl-1,10-phenanthroline (dphphen) (6)] were synthesized. The complexes were characterized by elemental analysis and spectroscopic techniques (IR, UV/Visible, and 1D and 2D NMR) and three of their X-ray structures were determined: {[}RuCl(PPh3)(Hdpa)(2)]Cl, {[}RuCl (PPh3)(Hdpa)(en)]Cl and {[}RuCl(PPh3)(Hdpa)(dmbipy)]Cl. All the complexes are more cytotoxic against the cancer cell line than against the non-tumor cell line, highlighting complexes 1 and 5, which have an index selectivity of 18 and 15, respectively. The binding constants of compounds 1-6 with human serum albumin (HSA) were determined by tryptophan fluorescence quenching, indicating moderate to strong interactions. The binding mode of the complexes to calf thymus (CT) DNA was explored by several techniques, which reveal that only the dphphen compound 6 causes distortions in the secondary and tertiary structures of DNA. The studies demonstrated that the nature of the N-N co-ligand and the presence of the PPh3 and Hdpa ligands are features that can influence the binding affinity of the complexes by the biomolecules and in the cytotoxic activity of the complexes. Overall, the complexes with diimine co-ligand are much more cytotoxic than compound 2 with the aliphatic diamine. (AU)

• FAPESP's process: 13/07581-9 - Design, Synthesis and Characterization of New Solid Forms of Anti-HIV Drugs.
• Grantee: Juan Carlos Tenorio Clavijo
• Support Opportunities: Scholarships in Brazil - Doctorate