Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cells

Ricardo G Teixeira; Ana Rita Brás; Leonor Côrte-Real; Rajendhraprasad Tatikonda; Anabela Sanches; M Paula Robalo; Fernando Avecilla; Tiago Moreira; M Helena Garcia; Matti Haukka; Ana Preto; Andreia Valente

doi:10.1016/j.ejmech.2017.11.059

Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cells

Eur J Med Chem. 2018 Jan 1:143:503-514. doi: 10.1016/j.ejmech.2017.11.059.

Affiliations

¹ Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
² Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal; Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Portugal, Campus de Gualtar, Braga 4710-057, Portugal.
³ Department of Chemistry, Nanoscience Center, University of Jyväskylä, P. O. Box 35, FI-40014 Jyväskylä, Finland.
⁴ Área Departamental de Engenharia Química, ISEL-Instituto Superior de Engenharia de Lisboa, Instituto Politécnico de Lisboa, Rua Conselheiro Emídio Navarro, 1, 1959-007 Lisboa, Portugal; Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
⁵ Grupo Xenomar, Centro de Investigacións Científicas Avanzadas (CICA), Departamento de Química, Facultade de Ciencias, Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain.
⁶ Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Portugal, Campus de Gualtar, Braga 4710-057, Portugal.
⁷ Centro de Química Estrutural, Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal. Electronic address: [email protected].

PMID: 29202411
DOI: 10.1016/j.ejmech.2017.11.059

Abstract

Three new compounds have been synthesized and completely characterized by analytical and spectroscopic techniques. The new bipyridine-perfluorinated ligand L1 and the new organometallic complex [Ru(η⁵-MeCp)(PPh₃)₂Cl] (Ru1) crystalize in the centrosymmetric triclinic space group P1¯. Analysis of the phenotypic effects induced by both organometallic complexes Ru1 and [Ru(η⁵-MeCp)(PPh₃)(L1)][CF₃SO₃] (Ru2), on human colorectal cancer cells (SW480 and RKO) survival, showed that Ru2 has a potent anti-proliferative activity, 4-6 times higher than cisplatin, and induce apoptosis in these cells. Data obtained in a noncancerous cell line derived from normal colon epithelial cells (NCM460) revealed an intrinsic selectivity of Ru2 for malignant cells at low concentrations, showing the high potential of this compound as a selective anticancer agent.

Keywords: Apoptosis; Colorectal cancer; Ruthenium methylcyclopentadienyl; Selectivity.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / pathology
Cycloparaffins / chemistry
Cycloparaffins / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Ligands
Molecular Structure
Organometallic Compounds / chemical synthesis
Organometallic Compounds / chemistry
Organometallic Compounds / pharmacology*
Pyridines / chemistry
Pyridines / pharmacology*
Ruthenium / chemistry
Ruthenium / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Cycloparaffins
Ligands
Organometallic Compounds
Pyridines
methylcyclopentadiene
Ruthenium