Publication Type Journal Article
Title Novel ruthenium cyclopentadienyl - peptide conjugate complexes against human FGFR(+) breast cancer
Authors J. Franco Machado Miguel Machuqueiro Fernanda M. Marques M Paula Robalo M.Fatima M.Piedade M. Helena Garcia Joao D. G. Correia Tânia S. Morais
Groups BIOIN BioMol
Journal DALTON TRANSACTIONS
Year 2020
Month May
Volume 49
Number 18
Pages 5974-5987
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 = eta(5)-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 eta(5)-cyclopentadienyl were synthesized, namely [Ru(eta(5)-C5H4COOH)(2,2 -bipy)(PPh3][CF3SO3] (TM281) and its precursors, [Ru(eta(5)-C5H4COOCH2CH3)(eta(2)-2,2 -bipy)(PPh3)][CF3SO3] (3) and [Ru(eta(5)-C5H4COOCH2CH3)(PPh3)(2)Cl] (2). Complex TM281 was prepared by the hydrolysis of the ethyl ester group appended to the eta(5)-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.
DOI http://dx.doi.org/10.1039/d0dt00955e
ISBN
Publisher
Book Title
ISSN 1477-9226
EISSN 1477-9234
Conference Name
Bibtex ID ISI:000534340700025
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