Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells
Background: Melanoma is the most aggressive and lethal skin cancer that affects thousands of people worldwide. Ruthenium complexes have shown promising results as cancer chemotherapeutics, offering several advantages over platinum drugs, such as potent efficacy, low toxicity, and less drug resistanc...
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MDPI AG
2025-01-01
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| author | Júlia S. M. Dias Guilherme A. Ferreira-Silva Rommel B. Viana João H. de Araujo Neto Javier Ellena Rodrigo S. Corrêa Marília I. F. Barbosa Marisa Ionta Antônio C. Doriguetto |
| author_facet | Júlia S. M. Dias Guilherme A. Ferreira-Silva Rommel B. Viana João H. de Araujo Neto Javier Ellena Rodrigo S. Corrêa Marília I. F. Barbosa Marisa Ionta Antônio C. Doriguetto |
| author_sort | Júlia S. M. Dias |
| collection | DOAJ |
| description | Background: Melanoma is the most aggressive and lethal skin cancer that affects thousands of people worldwide. Ruthenium complexes have shown promising results as cancer chemotherapeutics, offering several advantages over platinum drugs, such as potent efficacy, low toxicity, and less drug resistance. Additionally, anthraquinone derivatives have broad therapeutic applications, including melanoma. Objectives: Thus, two new ruthenium complexes with 1-hydroxy-9,10-anthraquinone were obtained: <i>trans-</i>[Ru(HQ)(PPh<sub>3</sub>)<sub>2</sub>(bipy)]PF<sub>6</sub> (<b>1</b>) and <i>cis-</i>[RuCl<sub>2</sub>(HQ)(dppb)] (<b>2</b>), where HQ = 1-hydroxy-9,10-anthraquinone, PPh<sub>3</sub> = triphenylphospine, bipy = 2,2′-bipyridine, PF<sub>6</sub> = hexafluorophosphate, and dppb = 1,4-bis(diphenylphosphine)butane. Methods: The complexes were characterized by infrared (IR), UV–vis, <sup>1</sup>H, <sup>13</sup>C{<sup>1</sup>H}, and <sup>31</sup>P{<sup>1</sup>H} NMR spectroscopies, molar conductivity, cyclic voltammetry, and elemental analysis. Furthermore, density functional theory (DFT) calculations were performed. Results: Compound (<b>2</b>) was determined by single-crystal X-ray diffraction, which confirms the bidentate coordination mode of HQ through the carbonyl and phenolate oxygens. Additionally, DNA-binding experiments yielded constants of 10<sup>5</sup> M<sup>−1</sup> (Kb = 6.93 × 10<sup>5</sup> for (<b>1</b>) and 1.60 × 10<sup>5</sup> for (<b>2</b>)) and demonstrate that both complexes can interact with DNA through intercalation, electrostatic attraction, or hydrogen bonding. Conclusions: The cytotoxicity profiles of the compounds were evaluated in human melanoma cell lines (SK-MEL-147, CHL-1, and WM1366), revealing greater cytotoxic activity for (<b>1</b>) on the CHL-1 cell line with an IC<sub>50</sub> of 14.50 ± 1.09 µM. Subsequent studies showed that (<b>1</b>) inhibits the proliferation of CHL-1 cells and induces apoptosis, associated at least in part with the pro-oxidant effect and cell cycle arrest at the G1/S transition. |
| format | Article |
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| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-9fec20987c084b2abba88b3b9c8bf6e82025-01-24T13:45:14ZengMDPI AGPharmaceuticals1424-82472025-01-011816310.3390/ph18010063Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma CellsJúlia S. M. Dias0Guilherme A. Ferreira-Silva1Rommel B. Viana2João H. de Araujo Neto3Javier Ellena4Rodrigo S. Corrêa5Marília I. F. Barbosa6Marisa Ionta7Antônio C. Doriguetto8Instituto de Química, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-000, MG, BrazilDepartamento de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-000, MG, BrazilDepartamento de Química, Universidade Estadual do Ceará (UECE), Limoeiro do Norte 62930-000, CE, BrazilInstituto de Química, Universidade de São Paulo (USP), São Paulo 05508-000, SP, BrazilInstituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos 13566-590, SP, BrazilDepartamento de Química, Universidade Federal de Ouro Preto (UFOP), Ouro Preto 35400-000, MG, BrazilInstituto de Química, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-000, MG, BrazilDepartamento de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-000, MG, BrazilInstituto de Química, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 37130-000, MG, BrazilBackground: Melanoma is the most aggressive and lethal skin cancer that affects thousands of people worldwide. Ruthenium complexes have shown promising results as cancer chemotherapeutics, offering several advantages over platinum drugs, such as potent efficacy, low toxicity, and less drug resistance. Additionally, anthraquinone derivatives have broad therapeutic applications, including melanoma. Objectives: Thus, two new ruthenium complexes with 1-hydroxy-9,10-anthraquinone were obtained: <i>trans-</i>[Ru(HQ)(PPh<sub>3</sub>)<sub>2</sub>(bipy)]PF<sub>6</sub> (<b>1</b>) and <i>cis-</i>[RuCl<sub>2</sub>(HQ)(dppb)] (<b>2</b>), where HQ = 1-hydroxy-9,10-anthraquinone, PPh<sub>3</sub> = triphenylphospine, bipy = 2,2′-bipyridine, PF<sub>6</sub> = hexafluorophosphate, and dppb = 1,4-bis(diphenylphosphine)butane. Methods: The complexes were characterized by infrared (IR), UV–vis, <sup>1</sup>H, <sup>13</sup>C{<sup>1</sup>H}, and <sup>31</sup>P{<sup>1</sup>H} NMR spectroscopies, molar conductivity, cyclic voltammetry, and elemental analysis. Furthermore, density functional theory (DFT) calculations were performed. Results: Compound (<b>2</b>) was determined by single-crystal X-ray diffraction, which confirms the bidentate coordination mode of HQ through the carbonyl and phenolate oxygens. Additionally, DNA-binding experiments yielded constants of 10<sup>5</sup> M<sup>−1</sup> (Kb = 6.93 × 10<sup>5</sup> for (<b>1</b>) and 1.60 × 10<sup>5</sup> for (<b>2</b>)) and demonstrate that both complexes can interact with DNA through intercalation, electrostatic attraction, or hydrogen bonding. Conclusions: The cytotoxicity profiles of the compounds were evaluated in human melanoma cell lines (SK-MEL-147, CHL-1, and WM1366), revealing greater cytotoxic activity for (<b>1</b>) on the CHL-1 cell line with an IC<sub>50</sub> of 14.50 ± 1.09 µM. Subsequent studies showed that (<b>1</b>) inhibits the proliferation of CHL-1 cells and induces apoptosis, associated at least in part with the pro-oxidant effect and cell cycle arrest at the G1/S transition.https://www.mdpi.com/1424-8247/18/1/631-hydroxy-9,10-anthraquinoneruthenium complexesmelanomaantiproliferative activity |
| spellingShingle | Júlia S. M. Dias Guilherme A. Ferreira-Silva Rommel B. Viana João H. de Araujo Neto Javier Ellena Rodrigo S. Corrêa Marília I. F. Barbosa Marisa Ionta Antônio C. Doriguetto Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells Pharmaceuticals 1-hydroxy-9,10-anthraquinone ruthenium complexes melanoma antiproliferative activity |
| title | Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells |
| title_full | Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells |
| title_fullStr | Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells |
| title_full_unstemmed | Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells |
| title_short | Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells |
| title_sort | ruthenium ii complex with 1 hydroxy 9 10 anthraquinone inhibits cell cycle progression at g0 g1 and induces apoptosis in melanoma cells |
| topic | 1-hydroxy-9,10-anthraquinone ruthenium complexes melanoma antiproliferative activity |
| url | https://www.mdpi.com/1424-8247/18/1/63 |
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