{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T12:19:35Z","timestamp":1767183575181,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00100\/2020; PTDC\/QUI-QIN\/28662\/2017; UID\/BIA\/04050\/2019; SFRH\/BD\/139412\/2018; SFRH\/BD\/139271\/2018; CEECIND\/01974\/2017; IF\/00069\/2014; IF\/00069\/2014\/CP1216\/CT0006; UID\/MULTI\/04046\/2019;"],"award-info":[{"award-number":["UIDB\/00100\/2020; PTDC\/QUI-QIN\/28662\/2017; UID\/BIA\/04050\/2019; SFRH\/BD\/139412\/2018; SFRH\/BD\/139271\/2018; CEECIND\/01974\/2017; IF\/00069\/2014; IF\/00069\/2014\/CP1216\/CT0006; UID\/MULTI\/04046\/2019;"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["LISBOA-01-0145-FEDER-028455 \/ PTDC\/QUI-QFI\/28455\/2017"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-028455 \/ PTDC\/QUI-QFI\/28455\/2017"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","award":["COST Action 17104 STRATAGEM"],"award-info":[{"award-number":["COST Action 17104 STRATAGEM"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A family of compounds with the general formula [Fe(\u03b75-C5H5)(CO)(PPh3)(NCR)]+ has been synthesized (NCR = benzonitrile (1); 4-hydroxybenzonitrile (2); 4-hydroxymethylbenzonitrile (3); 4-aminobenzonitrile (4); 4-bromobenzonitrile (5); and, 4-chlorocinnamonitrile (6)). All of the compounds were obtained in good yields and were completely characterized by standard spectroscopic and analytical techniques. Compounds 1, 4, and 5 crystallize in the monoclinc P21\/c space group and packing is determined by short contacts between the phosphane phenyl rings and cyclopentadienyl (compounds 1 and 4) or \u03c0-\u03c0 lateral interactions between the benzonitrile molecules (complex 5). 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 IC50 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 2 and 3, 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.<\/jats:p>","DOI":"10.3390\/molecules25071592","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T05:55:16Z","timestamp":1585893316000},"page":"1592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A New Family of Iron(II)-Cyclopentadienyl Compounds Shows Strong Activity against Colorectal and Triple Negative Breast Cancer Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Adhan","family":"Pilon","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"given":"Ana Rita","family":"Br\u00e1s","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus de Gualtar, Edif\u00edcio 18, 4710-057 Braga, Portugal"}]},{"given":"Leonor","family":"C\u00f4rte-Real","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"given":"Fernando","family":"Avecilla","sequence":"additional","affiliation":[{"name":"Grupo Xenomar, Centro de Investigaci\u00f3ns Cient\u00edficas Avanzadas (CICA), Departamento de Qu\u00edmica, Facultade de Ciencias, Universidade da Coru\u00f1a, Campus de A Coru\u00f1a, 15071 A Coru\u00f1a, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0492-6666","authenticated-orcid":false,"given":"Paulo J.","family":"Costa","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, University of Lisboa, BioISI\u2014Biosystems &amp; Integrative Sciences Institute, Campo Grande, C8 bdg, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-0630","authenticated-orcid":false,"given":"Ana","family":"Preto","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus de Gualtar, Edif\u00edcio 18, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-2218","authenticated-orcid":false,"given":"M. Helena","family":"Garcia","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]},{"given":"Andreia","family":"Valente","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1021\/cr400460s","article-title":"Metallodrugs in medicinal inorganic chemistry","volume":"114","author":"Mjos","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1039\/C5NJ01449B","article-title":"Recent advances in iron complexes as potential anticancer agents","volume":"40","author":"Wani","year":"2016","journal-title":"New J. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1039\/C8DT03440K","article-title":"Ferrocene-appended pharmacophores: An exciting approach for modulating the biological potential of organic scaffolds","volume":"48","author":"Singh","year":"2019","journal-title":"Dalton Trans."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9824","DOI":"10.1039\/C8DT01582A","article-title":"Ferrocifens labelled with an infrared rhenium tricarbonyl tag: Synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells","volume":"47","author":"Wang","year":"2018","journal-title":"Dalton Trans."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.phrs.2017.01.031","article-title":"Efficient ferrocifen anticancer drug and Bcl-2 gene therapy using lipid nanocapsules on human melanoma xenograft in mouse","volume":"126","author":"Resnier","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S0022-328X(01)00953-6","article-title":"Studies on organometallic selective estrogen receptor modulators. (SERMs) Dual activity in the hydroxy-ferrocifen series","volume":"637","author":"Top","year":"2001","journal-title":"J. Organomet. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0022-328X(97)00086-7","article-title":"Facile route to ferrocifen, 1-[4-(2-dimethylaminoethoxy)]-1-(phenyl-2-ferrocenyl-but-1-ene), first organometallic analogue of tamoxifen, by the McMurry reaction","volume":"541","author":"Top","year":"1997","journal-title":"J. Organomet. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jinorgbio.2014.08.015","article-title":"Ferrocifen derivatives that induce senescence in cancer cells: Selected examples","volume":"141","author":"Mathieu","year":"2014","journal-title":"J. Inorg. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ijpharm.2009.05.031","article-title":"Dose effect activity of ferrocifen-loaded lipid nanocapsules on a 9L-glioma model","volume":"379","author":"Allard","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"527","DOI":"10.4155\/fmc.16.7","article-title":"Tracking antitumor metallodrugs: Promising agents with the Ru (II)- and Fe (II)-cyclopentadienyl scaffolds","volume":"8","author":"Morais","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9135","DOI":"10.1021\/acs.inorgchem.9b00735","article-title":"Ruthenium-Cyclopentadienyl Bipyridine-Biotin Based Compounds: Synthesis and Biological Effect","volume":"58","author":"Karas","year":"2019","journal-title":"Inorg. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jinorgbio.2013.07.002","article-title":"First polymer \u201cruthenium-cyclopentadienyl\u201d complex as potential anticancer agent","volume":"127","author":"Valente","year":"2013","journal-title":"J. Inorg. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jinorgbio.2015.06.015","article-title":"The key role of coligands in novel ruthenium (II)-cyclopentadienyl bipyridine derivatives: Ranging from non-cytotoxic to highly cytotoxic compounds","volume":"150","author":"Marques","year":"2015","journal-title":"J. Inorg. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.ejmech.2019.02.061","article-title":"Polymer \u201cruthenium-cyclopentadienyl\u201d conjugates\u2014New emerging anti-cancer drugs","volume":"168","author":"Moreira","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.ejmech.2018.12.022","article-title":"Unprecedented inhibition of P-gp activity by a novel ruthenium- cyclopentadienyl compound bearing a bipyridine-biotin ligand","volume":"163","author":"Karas","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s00775-014-1120-y","article-title":"Anticancer activity of structurally related ruthenium(II) cyclopentadienyl complexes","volume":"19","author":"Mendes","year":"2014","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.ejmech.2017.11.059","article-title":"Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cells","volume":"143","author":"Teixeira","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jinorgbio.2013.07.033","article-title":"Important cytotoxicity of novel iron(II) cyclopentadienyl complexes with imidazole based ligands","volume":"129","author":"Morais","year":"2013","journal-title":"J. Inorg. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jorganchem.2014.01.027","article-title":"New iron (II) cyclopentadienyl derivative complexes: Synthesis and antitumor activity against human leukemia cancer cells","volume":"756","author":"Valente","year":"2014","journal-title":"J. Organomet. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jorganchem.2017.10.004","article-title":"New iron cyclopentadienyl complexes bearing different phosphane co-ligands: Structural factors vs. cytotoxicity","volume":"852","author":"Pilon","year":"2017","journal-title":"J. Organomet. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18814","DOI":"10.1039\/C5RA23891A","article-title":"Cyclopentadienyl iron dicarbonyl (CpFe (CO)2) derivatives as apoptosis-inducing agents","volume":"6","author":"Poh","year":"2016","journal-title":"RSC Adv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14801","DOI":"10.1002\/chem.201902885","article-title":"Anticancer Potential of Diiron Vinyliminium Complexes","volume":"25","author":"Rocco","year":"2019","journal-title":"Chem. A Eur. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1021\/ic50041a022","article-title":"Chemistry of the Cyclopentadienylmetal Carbonyls. II. Cyclopentadienyliron Carbonyl Derivatives","volume":"5","author":"Treichel","year":"1966","journal-title":"Inorg. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ic50039a037","article-title":"Reactions of Cyclopentadienyl (methyl)iron Dicarbonyl with Various Ligands. Cyclopentadienyl (acetyl)iron Carbonyl Phosphine and Phosphite Complexes","volume":"5","author":"Bibler","year":"1966","journal-title":"Inorg. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.1016\/j.jorganchem.2005.06.020","article-title":"Tertiary phosphine induced migratory carbonyl insertion in cyclopentadienyl complexes of iron (II)","volume":"690","author":"Makunya","year":"2005","journal-title":"J. Organomet. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.bjp.2015.02.009","article-title":"Cytotoxicity screening of essential oils in cancer cell lines","volume":"25","author":"Alves","year":"2015","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1021\/acs.jmedchem.5b00403","article-title":"Cyclopentadienyl-ruthenium (II) and iron (II) organometallic compounds with carbohydrate derivative ligands as good colorectal anticancer agents","volume":"58","author":"Florindo","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/0022-1902(56)80102-4","article-title":"Cyclopentadienyl-nitric oxide compounds of chromium and manganese","volume":"2","author":"Piper","year":"1956","journal-title":"J. Inorg. Nucl. Chem."},{"key":"ref_29","unstructured":"Sheldrick, G.M. (2004). SADABS, Version 2.10, University of G\u00f6ttingen."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal structure refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. C Struct. Chem."},{"key":"ref_31","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalman, G., Barone, V., Mennucci, B., and Petersson, G.A. (2009). Gaussian09, Revision D.01, Gaussian, Inc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6158","DOI":"10.1063\/1.478522","article-title":"Toward reliable density functional methods without adjustable parameters: The PBE0 model","volume":"110","author":"Adamo","year":"1999","journal-title":"J. Chem. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1002\/(SICI)1096-987X(199610)17:13<1571::AID-JCC9>3.0.CO;2-P","article-title":"The role of databases in support of computational chemistry calculations","volume":"17","author":"Feller","year":"1996","journal-title":"J. Comput. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1021\/ci600510j","article-title":"Basis set exchange: A community database for computational sciences","volume":"47","author":"Schuchardt","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.1021\/jp810292n","article-title":"Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions","volume":"113","author":"Marenich","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"ref_36","first-page":"839","article-title":"Software News and Updates cclib: A Library for Package-Independent Computational Chemistry Algorithms","volume":"29","author":"Tenderholt","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/BF02722955","article-title":"NCM460, a normal human colon mucosal epithelial cell line","volume":"32","author":"Moyer","year":"1996","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Mor\u00e1n, O.A., Villarreal, M.L., \u00c1lvarez-Berber, L., Meneses-Acosta, A., and Rodr\u00edguez-L\u00f3pez, V. (2016). Cytotoxicity, post-treatment recovery, and selectivity analysis of naturally occurring podophyllotoxins from Bursera fagaroides var. fagaroides on breast cancer cell lines. Molecules, 21.","DOI":"10.3390\/molecules21081013"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/7\/1592\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:13:36Z","timestamp":1760174016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/7\/1592"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["molecules25071592"],"URL":"https:\/\/doi.org\/10.3390\/molecules25071592","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2020,3,30]]}}}