PUBLICATION
Synthesis, characterization and biological evaluation of cationic organoruthenium(ii) fluorene complexes: influence of the nature of the counteranion
- Authors
- Haghdoost, M.M., Golbaghi, G., Guard, J., Sielanczyk, S., Patten, S.A., Castonguay, A.
- ID
- ZDB-PUB-190822-8
- Date
- 2019
- Source
- Dalton transactions (Cambridge, England : 2003) 48(35): 13396-13405 (Journal)
- Registered Authors
- Patten, Shumoogum
- Keywords
- none
- MeSH Terms
-
- Animals
- Antineoplastic Agents/chemical synthesis
- Antineoplastic Agents/chemistry*
- Antineoplastic Agents/pharmacology*
- Antineoplastic Agents/toxicity
- Cell Proliferation/drug effects
- Chemistry Techniques, Synthetic
- Coordination Complexes/chemical synthesis
- Coordination Complexes/chemistry*
- Coordination Complexes/pharmacology*
- Coordination Complexes/toxicity
- Fluorenes/chemistry*
- Humans
- MCF-7 Cells
- Models, Molecular
- Molecular Conformation
- Ruthenium/chemistry*
- Zebrafish/embryology
- PubMed
- 31432885 Full text @ Dalton Trans.
Citation
Haghdoost, M.M., Golbaghi, G., Guard, J., Sielanczyk, S., Patten, S.A., Castonguay, A. (2019) Synthesis, characterization and biological evaluation of cationic organoruthenium(ii) fluorene complexes: influence of the nature of the counteranion. Dalton transactions (Cambridge, England : 2003). 48(35):13396-13405.
Abstract
In this study, five ruthenium arene complexes with fluorene-bearing N,N-(1) and N,O-(2) donor Schiff base ligands were synthesized and fully characterized. Cationic ruthenium complexes 3[X], ([Ru(η6-C6H6)(Cl)(fluorene-N[double bond, length as m-dash]CH-pyridine)][X] (where X = BF4, PF6, BPh4), were obtained by reacting ligand 1 with [Ru(η6-C6H6)Cl2]2 in the presence of NH4X salts, whereas neutral complex 4, Ru(η6-C6H6)(Cl)(fluorene-N[double bond, length as m-dash]CH-naphtholate), was isolated by reacting ligand 2 with the same precursor. It was possible to obtain a cationic version of the latter, 5[BF4], by reacting 4 with AgBF4 in the presence of pyridine. All compounds were fully characterized by NMR and HR-ESI-MS whereas some of them were also analyzed by single crystal X-ray analysis. Their in vitro antiproliferative activity was also assessed in human breast cancer cell lines, notably MCF-7 and T47D. Complex 4 and its cationic counterpart 5[BF4] were found to be the most cytotoxic compounds of the series (IC50 = 6.2-16.2 μM) and displayed higher antiproliferative activities than cisplatin in both cell lines. It was found that 5[BF4] undergoes a ligand exchange reaction and readily converts to 4 in the presence of 0.1 M NaCl, explaining the similarity in their observed cytotoxicities. Whereas 3[BF4] and 3[PF6] were found inactive at the tested concentrations, 3[BPh4] displayed a considerable cytotoxicity (IC50 = 16.7-27.8 μM). Notably, 3[BPh4], 4 (and 5[BF4]) were active against T47D, a cisplatin resistant cell line. Interestingly, 4 (16.4 μM) was found to be less cytotoxic than 3[BPh4] and cisplatin (6.6 and 7.9 μM, respectively) in breast healthy cells (MCF-12A). However, in comparison to 4 and cisplatin (at 10 μM), a lower in vivo toxicity was observed for complex 3[BPh4] on the development of zebrafish (Danio rerio) embryos.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping