Loading…

The choice of μ-vinyliminium ligand substituents is key to optimize the antiproliferative activity of related diiron complexes

Abstract Diiron vinyliminium complexes constitute a large family of organometallics displaying a promising anticancer potential. The complexes [Fe2Cp2(CO)(μ-CO){μ-η1:η3-C(R3)C(R4)CN(R1)(R2)}]CF3SO3 (2a-c, 4a-d) were synthesized, assessed for their behavior in aqueous solutions (D2O solubility, Log P...

Full description

Saved in:
Bibliographic Details
Published in:Metallomics 2023-01, Vol.15 (1)
Main Authors: Campanella, Beatrice, Braccini, Simona, Bresciani, Giulio, De Franco, Michele, Gandin, Valentina, Chiellini, Federica, Pratesi, Alessandro, Pampaloni, Guido, Biancalana, Lorenzo, Marchetti, Fabio
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Diiron vinyliminium complexes constitute a large family of organometallics displaying a promising anticancer potential. The complexes [Fe2Cp2(CO)(μ-CO){μ-η1:η3-C(R3)C(R4)CN(R1)(R2)}]CF3SO3 (2a-c, 4a-d) were synthesized, assessed for their behavior in aqueous solutions (D2O solubility, Log Pow, stability in D2O/Me2SO-d6 mixture at 37°C over 48 h) and investigated for their antiproliferative activity against A2780 and A2780cisR ovarian cancer cell lines and the nontumoral one Balb/3T3 clone A31. Cytotoxicity data collected for 50 vinyliminium complexes were correlated with the structural properties (i.e. the different R1–R4 substituents) using the partial least squares methodology. A clear positive correlation emerged between the octanol–water partition coefficient and the relative antiproliferative activity on ovarian cancer cell lines, both of which appear as uncorrelated to the cancer cell selectivity. However, the different effects played by the R1–R4 substituents allow tracing guidelines for the development of novel, more effective compounds. Based on these results, three additional complexes (4p-r) were designed, synthesized and biologically investigated, revealing their ability to hamper thioredoxin reductase enzyme and to induce cancer cell production of reactive oxygen species. Graphical Abstract Graphical Abstract A joint synthetic, spectroscopic, biological and chemometric study is presented aimed to identify the best vinyliminium ligand substituents (R1–4) for optimal cytotoxicity profile of diiron complexes.
ISSN:1756-591X
1756-591X
DOI:10.1093/mtomcs/mfac096