Novel "ruthenium cyclopentadienyl"–peptide conjugate complexes against human FGFR(+) breast cancer. Issue 18 (21st April 2020)

• Record Type: Journal Article
• Authors: Franco Machado, João; Machuqueiro, Miguel; Marques, Fernanda; Robalo, M. Paula; Piedade, M. Fátima M.; Garcia, M. Helena; Correia, João D. G.; Morais, Tânia S.
• Is Part Of: Dalton transactions. Volume 49:Issue 18(2020)
• Page Start: 5974
• Page End: 5987
• Publication Date: 2020-04-21
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d0dt00955e
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Synthesis of the first half-sandwich ruthenium(ii )-cyclopentadienyl peptide conjugates and their biological evaluation against human FGFR(+) and FGFR(−) breast cancer cells. Abstract : In this work we explored the possibility of improving the selectivity of a cytotoxic Ru complex [RuCp(PPh3 )(2, 2′-bipy)][CF3 SO3 ] (where Cp = η 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 η 5 -cyclopentadienyl were synthesized, namely [Ru(η 5 -C5 H4 COOH)(2, 2′-bipy)(PPh3 )][CF3 SO3 ] (TM281 ) and its precursors, [Ru(η 5 -C5 H4 COOCH2 CH3 )(η 2 -2, 2′-bipy)(PPh3 )][CF3 SO3 ] (3 ) and [Ru(η 5 -C5 H4 COOCH2 CH3 )(PPh3 )2 Cl] (2 ). Complex TM281 was prepared by the hydrolysis of the ethyl ester group appended to the η 5 -cyclopentadienyl ligand of complex 3 with K2 CO3 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 P 21/ 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.