Jump to main content
Jump to site search

Issue 18, 2020
Previous Article Next Article

Novel “ruthenium cyclopentadienyl”–peptide conjugate complexes against human FGFR(+) breast cancer

Author affiliations

Abstract

In this work we explored the possibility of improving the selectivity of a cytotoxic Ru complex [RuCp(PPh3)(2,2′-bipy)][CF3SO3] (where Cp = η5-cyclopentadienyl) TM34 towards FGFR(+) breast cancer cells. Molecular dynamics (MD) simulations of TM34 in a phosphatidylcholine membrane model pinpointed the cyclopentadienyl group as a favorable derivatization position for the peptide conjugation approach. Three new Ru(II) complexes presenting a functionalized η5-cyclopentadienyl were synthesized, namely [Ru(η5-C5H4COOH)(2,2′-bipy)(PPh3)][CF3SO3] (TM281) and its precursors, [Ru(η5-C5H4COOCH2CH3)(η2-2,2′-bipy)(PPh3)][CF3SO3] (3) and [Ru(η5-C5H4COOCH2CH3)(PPh3)2Cl] (2). Complex TM281 was prepared by the hydrolysis of the ethyl ester group appended to the η5-cyclopentadienyl ligand of complex 3 with K2CO3 in water/acetonitrile, followed by mild protonation using an ion exchange resin. The newly synthesized complexes were fully characterized by NMR, FTIR and UV-vis spectroscopic techniques. Also, electrochemical studies were carried out by means of cyclic voltammetry in order to evaluate the stability of the compounds. Single crystal X-ray diffraction studies were carried out for compounds 3 and TM281 which crystallized in the monoclinic system, space group P21/n. The unprecedented synthesis and characterization of three half-sandwich ruthenium(II)-cyclopentadienyl peptide conjugates and their preliminary biological evaluation against human FGFR(+) and FGFR(−) breast cancer cells are also reported.

Graphical abstract: Novel “ruthenium cyclopentadienyl”–peptide conjugate complexes against human FGFR(+) breast cancer

Back to tab navigation

Supplementary files

Article information


Submitted
13 Mar 2020
Accepted
05 Apr 2020
First published
07 Apr 2020

Dalton Trans., 2020,49, 5974-5987
Article type
Paper

Novel “ruthenium cyclopentadienyl”–peptide conjugate complexes against human FGFR(+) breast cancer

J. Franco Machado, M. Machuqueiro, F. Marques, M. P. Robalo, M. F. M. Piedade, M. H. Garcia, J. D. G. Correia and T. S. Morais, Dalton Trans., 2020, 49, 5974
DOI: 10.1039/D0DT00955E

Social activity

Search articles by author

Spotlight

Advertisements