0554906 - BFÚ 2022 RIV US eng J - Journal Article
Biancalana, L. - Kostrhunová, Hana - Batchelor, L. - Hadiji, M. - Degano, I. - Pampaloni, G. - Zacchini, S. - Dyson, P.J. - Brabec, Viktor - Marchetti, F.
Hetero-Bis-Conjugation of Bioactive Molecules to Half-Sandwich Ruthenium(II) and Iridium(III) Complexes Provides Synergic Effects in Cancer Cell Cytotoxicity.
Inorganic Chemistry. Roč. 60, č. 13 (2021), s. 9529-9541. ISSN 0020-1669. E-ISSN 1520-510X
R&D Projects: GA ČR(CZ) GC20-14082J
Institutional support: RVO:68081707
Keywords : anticancer agents * platinum(iv) prodrug * crystal-structure * rational design * acid * derivatives
OECD category: Organic chemistry
Impact factor: 5.436, year: 2021 ; AIS: 0.808, rok: 2021
Method of publishing: Limited access
Result website:
https://pubs.acs.org/doi/10.1021/acs.inorgchem.1c00641DOI: https://doi.org/10.1021/acs.inorgchem.1c00641

Four bipyridine-type ligands variably derivatized with two bioactive groups (taken from ethacrynic acid, flurbiprofen, biotin, and benzylpenicillin) were prepared via sequential esterification steps from commercial 2,2'-bipyridine-4,4'-dicarboxylic acid and subsequently coordinated to ruthenium(II) p-cymene and iridium(III) pentamethylcyclopentadienyl scaffolds. The resulting complexes were isolated as nitrate salts in high yields and fully characterized by analytical and spectroscopic methods. NMR and MS studies in aqueous solution and in cell culture medium highlighted a substantial stability of ligand coordination and a slow release of the bioactive fragments in the latter case. The complexes were assessed for their antiproliferative activity on four cancer cell lines, showing cytotoxicity to the low micromolar level (equipotent with cisplatin). Additional biological experiments revealed a multimodal mechanism of action of the investigated compounds, involving DNA metalation and enzyme inhibition. Synergic effects provided by specific combinations of metal and bioactive fragments were identified, pointing toward an optimal ethacrynic acid/flurbiprofen combination for both Ru(II) and Ir(III) complexes.
Permanent Link: http://hdl.handle.net/11104/0329521