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https://hdl.handle.net/1822/64877
Título: | A new family of iron(II)-cyclopentadienyl compounds shows strong activity against colorectal and triple negative breast cancer cells |
Autor(es): | Pilon, Adhan Brás, Ana Rita Côrte-Real, Leonor Avecilla, Fernando Costa, Paulo J. Preto, Ana Garcia, M. Helena Valente, Andreia |
Palavras-chave: | iron(II)-cyclopentadienyl nitrile-based ligands colorectal cancer triple negative breast cancer |
Data: | 30-Mar-2020 |
Editora: | Multidisciplinary Digital Publishing Institute |
Revista: | Molecules |
Citação: | Pilon, A.; Brás, A.R.; Côrte-Real, L.; Avecilla, F.; Costa, P.J.; Preto, A.; Garcia, M.H.; Valente, A. A New Family of Iron(II)-Cyclopentadienyl Compounds Shows Strong Activity against Colorectal and Triple Negative Breast Cancer Cells. Molecules 2020, 25, 1592. |
Resumo(s): | A family of compounds with the general formula [Fe(η<sup>5</sup>-C<sub>5</sub>H<sub>5</sub>)(CO)(PPh<sub>3</sub>)(NCR)]<sup>+</sup> has been synthesized (NCR = benzonitrile (<b>1</b>); 4-hydroxybenzonitrile (<b>2</b>); 4-hydroxymethylbenzonitrile (<b>3</b>); 4-aminobenzonitrile (<b>4</b>); 4-bromobenzonitrile (<b>5</b>); and, 4-chlorocinnamonitrile (<b>6</b>)). All of the compounds were obtained in good yields and were completely characterized by standard spectroscopic and analytical techniques. Compounds <b>1</b>, <b>4</b>, and <b>5</b> crystallize in the monoclinc P21/c space group and packing is determined by short contacts between the phosphane phenyl rings and cyclopentadienyl (compounds <b>1</b> and <b>4</b>) or π-π lateral interactions between the benzonitrile molecules (complex <b>5</b>). DFT and TD-DFT calculations were performed to help in the interpretation of the experimental UV-Vis. data and assign the electronic transitions. Cytotoxicity studies in MDA-MB-231 breast and SW480 colorectal cancer-derived cell lines showed IC<sub>50</sub> values at a low micromolar range for all of the compounds in both cell lines. The determination of the selectivity index for colorectal cells (SW480 vs. NCM460, a normal colon-derived cell line) indicates that the compounds have some inherent selectivity. Further studies on the SW480 cell line demonstrated that the compounds induce cell death by apoptosis, inhibit proliferation by inhibiting the formation of colonies, and affect the actin-cytoskeleton of the cells. These results are not observed for the hydroxylated compounds <b>2</b> and <b>3</b>, where an alternative mode of action might be present. Overall, the results indicate that the substituent at the nitrile-based ligand is associated to the biological activity of the compounds. |
Tipo: | Artigo |
Descrição: | The following is available online, Figure S1—1H NMR spectrum of complexes 6, in acetone-d6, Table S1. Bond lengths [Å] and angles [°] for [Fe(η5-Cp)(CO)(PhCN)(PPh3)][CF3SO3] 1, [Fe(η5-Cp)(CO)(p-NCPhNH2)(PPh3)][CF3SO3] 4 and [Fe(η5-Cp)(CO)(p-NCPhBr)(PPh3)][CF3SO3] 5, Table S2. Relevant TD-DFT (PBE0) excitation energies (λ), oscillator strengths (f) and compositions (only those > 5% are shown), for complexes 1–6, compared with experimental data (λexp). Both calculated and experimental values were obtained in dichloromethane, Figure S2—UV-Vis spectra of complexes 1–6 in DMSO along the 24 h study, Figure S3—UV-Vis spectra of complexes 1–6 in DMSO/DMEM mixture along the 24 h study and its variation plot (%) (bottom), Figure S4. ‘FeCp’ compounds affect the colony formation ability of SW480 cell line. Analysis of the colony formation ability, after 48 h of incubation with 1/4 IC50 and IC50, in SW480 cell line. Representative images of colony formation assay in SW480 cell line, Figure S5. ‘FeCp’ compounds induce apoptosis colorectal cancer-derived cell line. Apoptotic cell death was analyzed by Annexin V fluorescein isothiocyanate (AV-FITC) and propidium iodide (PI) assay in SW480 cells, after incubation with IC50 and 2×IC50 concentrations for 48 h. Representative histograms of SW480 cell line double stained with AV and PI, Table S4. Crystal data and structure refinement for [Fe(η5-Cp)(CO)(PhCN)(PPh3)][CF3SO3] 1, [Fe(η5-Cp)(CO)(p-NCPhNH2)(PPh3)][CF3SO3] 4 and [Fe(η5-Cp)(CO)(p-NCPhBr)(PPh3)][CF3SO3] 5. |
URI: | https://hdl.handle.net/1822/64877 |
DOI: | 10.3390/molecules25071592 |
e-ISSN: | 1420-3049 |
Versão da editora: | https://www.mdpi.com/1420-3049/25/7/1592 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | DBio - Artigos/Papers |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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molecules-25-01592-v3.pdf | 5,17 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons