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
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.
Book Title
ISSN 1477-9226
EISSN 1477-9234
Conference Name
Bibtex ID ISI:000534340700025
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