A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R} Complexes with Variable R Groups
Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/14/7422 |
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| author | Alice De Palo Dijana Draca Maria Grazia Murrali Stefano Zacchini Guido Pampaloni Sanja Mijatovic Danijela Maksimovic-Ivanic Fabio Marchetti |
| author_facet | Alice De Palo Dijana Draca Maria Grazia Murrali Stefano Zacchini Guido Pampaloni Sanja Mijatovic Danijela Maksimovic-Ivanic Fabio Marchetti |
| author_sort | Alice De Palo |
| collection | DOAJ |
| description | Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R)Cl(μ-Cl)]<sub>2</sub> (R = Me, <b>1a</b>; R = H, <b>1b</b>; R = Pr, <b>1c</b>; R = 4-C<sub>6</sub>H<sub>4</sub>F, <b>1d</b>; R = 4-C<sub>6</sub>H<sub>4</sub>OH, <b>1e</b>), their 2-phenylpyridyl mononuclear derivatives [Ir(η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R)(k<i><sub>N</sub></i>,k<i><sub>C</sub></i>PhPy)Cl] (<b>2a–d</b>), and the dimethylsulfoxide complex [Ir{η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>(4-C<sub>6</sub>H<sub>4</sub>OH)}Cl<sub>2</sub>(κ<i><sub>S</sub></i>-Me<sub>2</sub>S=O)] (<b>3</b>) were synthesized, structurally characterized, and assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5). Complexes <b>2b</b> (R = H) and <b>2d</b> (4-C<sub>6</sub>H<sub>4</sub>F) emerged as the most active ones and were selected for further investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumoricidal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species. |
| first_indexed | 2024-03-10T09:37:41Z |
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| issn | 1661-6596 1422-0067 |
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| last_indexed | 2024-03-10T09:37:41Z |
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| spelling | doaj.art-d8ca13f483174089b04c96e935c77f272023-11-22T03:58:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214742210.3390/ijms22147422A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R} Complexes with Variable R GroupsAlice De Palo0Dijana Draca1Maria Grazia Murrali2Stefano Zacchini3Guido Pampaloni4Sanja Mijatovic5Danijela Maksimovic-Ivanic6Fabio Marchetti7Department of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, I-56124 Pisa, ItalyDepartment of Immunology, Institute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, SerbiaDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, I-56124 Pisa, ItalyDepartment of Industrial Chemistry “Toso Montanari”, University of Bologna, Viale Risorgimento 4, I-40136 Bologna, ItalyDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, I-56124 Pisa, ItalyDepartment of Immunology, Institute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, SerbiaDepartment of Immunology, Institute for Biological Research “Sinisa Stankovic”—National Institute of Republic of Serbia, University of Belgrade, 11060 Belgrade, SerbiaDepartment of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, I-56124 Pisa, ItalyPiano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*) have been intensively investigated as anticancer drug candidates and hold much promise in this setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the antiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R)Cl(μ-Cl)]<sub>2</sub> (R = Me, <b>1a</b>; R = H, <b>1b</b>; R = Pr, <b>1c</b>; R = 4-C<sub>6</sub>H<sub>4</sub>F, <b>1d</b>; R = 4-C<sub>6</sub>H<sub>4</sub>OH, <b>1e</b>), their 2-phenylpyridyl mononuclear derivatives [Ir(η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R)(k<i><sub>N</sub></i>,k<i><sub>C</sub></i>PhPy)Cl] (<b>2a–d</b>), and the dimethylsulfoxide complex [Ir{η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>(4-C<sub>6</sub>H<sub>4</sub>OH)}Cl<sub>2</sub>(κ<i><sub>S</sub></i>-Me<sub>2</sub>S=O)] (<b>3</b>) were synthesized, structurally characterized, and assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5). Complexes <b>2b</b> (R = H) and <b>2d</b> (4-C<sub>6</sub>H<sub>4</sub>F) emerged as the most active ones and were selected for further investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumoricidal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.https://www.mdpi.com/1422-0067/22/14/7422bioorganometallic chemistryorganoiridium complexescytotoxicityapoptosissenescencecell proliferation |
| spellingShingle | Alice De Palo Dijana Draca Maria Grazia Murrali Stefano Zacchini Guido Pampaloni Sanja Mijatovic Danijela Maksimovic-Ivanic Fabio Marchetti A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R} Complexes with Variable R Groups International Journal of Molecular Sciences bioorganometallic chemistry organoiridium complexes cytotoxicity apoptosis senescence cell proliferation |
| title | A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R} Complexes with Variable R Groups |
| title_full | A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R} Complexes with Variable R Groups |
| title_fullStr | A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R} Complexes with Variable R Groups |
| title_full_unstemmed | A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R} Complexes with Variable R Groups |
| title_short | A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η<sup>5</sup>-C<sub>5</sub>Me<sub>4</sub>R} Complexes with Variable R Groups |
| title_sort | comparative analysis of the in vitro anticancer activity of iridium iii η sup 5 sup c sub 5 sub me sub 4 sub r complexes with variable r groups |
| topic | bioorganometallic chemistry organoiridium complexes cytotoxicity apoptosis senescence cell proliferation |
| url | https://www.mdpi.com/1422-0067/22/14/7422 |
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