| Full text | |
| Author(s): |
Silva, Camila F. N.
[1]
;
Barbosa Ramos, Loyanne Carla
[2]
;
Rohrabaugh, Thomas N.
[3]
;
Vandevord, Jessica M.
[3]
;
da Silva, Roberto Santana
[2]
;
Turro, Claudia
[3]
;
Nikolaou, Sofia
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
[3] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 - USA
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | Inorganic Chemistry Communications; v. 114, APR 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
This work evaluates the cytotoxicity of {[}Ru-3(mu(3)-O)(mu-OAc)(5)[mu-eta(1)(C),eta(2)(N,N)-phen](Py)(2)](PF6 ) (1), a triruthenium acetate cluster combined with an ortho-metallated 1,10-phenanthroline (phen) ligand, along with its interactions with biomolecules. In vitro cytotoxicity tests against the B16F10 (murine melanoma) and L929 (fibroblast) cell lines showed that 1 decreased cancer cell viability by 50% at 25 mu M, while it requires 50 mu M of free phen ligand to achieve the same effect. Importantly, 1 is not active against non-tumor cell model L929 up to 100 pM. Spectrophotometric titrations suggest that 1 and DNA interacted weakly through electrostatic attraction and semi-intercalation. Despite the presence of a planar and aromatic ligand, relative viscosity measurements are not consistent with the DNA intercalation of 1, presumably due to the small size of phenanthroline. The proteinbinding ability of compound 1 was evaluated using human serum albumin (HSA) as a model and monitored by spectroscopic techniques, including steady-state emission and absorption, time-resolved luminescence, and circular dichroism, CD. Compound 1 quenches the HSA emission efficiently (K-ap = 4.72 x 10(8) M-1, 298 K) mostly by static quenching, consistent with its relatively strong binding to HSA (K-b = 3.70 x 10 6 M-1, 298 K). Analysis of AH and AS values (604 kJ/mol and 2162 J/mol K, respectively) suggest the contribution of hydrophobic interactions. CD measurements demonstrated that the protein a-helical structure decreased in the presence of I, indicating a partial conformation change of HSA. Although the interaction of 1 with DNA is weak, its binding to the model protein HSA is strong, such that the cytotoxicity of the complex may be attributed to protein-complex interactions. This work provides a framework to design new triruthenium acetates to achieve stronger and more selective binding to biomolecules. Importantly, the selective activity of 1 towards a cancer cell line, while remaining inactive against healthy cells, represents a critical finding for the design of new cancer therapeutics based on triruthenium acetate clusters. (AU) | |
| FAPESP's process: | 17/15202-9 - Photochemical research and systematic in vitro study of the interaction mechanisms in novel trinuclear ruthenium complexes with DNA using different techniques |
| Grantee: | Camila Fontes Neves da Silva |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 14/25561-8 - Trinuclear ruthenium carboxylates with functional ligands CO, NO and intercalators: chemical study and interactions with biomolecules target |
| Grantee: | Camila Fontes Neves da Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 18/18060-3 - Use of inorganic supramolecular structures for the development of functional molecules and controlled release of bioactive species |
| Grantee: | Sofia Nikolaou |
| Support Opportunities: | Regular Research Grants |