Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents
Cisplatin-type covalent chemotherapeutics are a cornerstone of modern medicinal oncology. However, these drugs remain encumbered with dose-limiting side effects and are susceptible to innate and acquired resistance. The bulk of platinum anticancer research has focused on Cisplatin and its derivative...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/24/17150 |
| _version_ | 1797380787110150144 |
|---|---|
| author | Brondwyn S. McGhie Jennette Sakoff Jayne Gilbert Christopher P. Gordon Janice R. Aldrich-Wright |
| author_facet | Brondwyn S. McGhie Jennette Sakoff Jayne Gilbert Christopher P. Gordon Janice R. Aldrich-Wright |
| author_sort | Brondwyn S. McGhie |
| collection | DOAJ |
| description | Cisplatin-type covalent chemotherapeutics are a cornerstone of modern medicinal oncology. However, these drugs remain encumbered with dose-limiting side effects and are susceptible to innate and acquired resistance. The bulk of platinum anticancer research has focused on Cisplatin and its derivatives. Here, we take inspiration from the design of platinum complexes and ligands used successfully with other metals to create six novel complexes. Herein, the synthesis, characterization, DNA binding affinities, and lipophilicity of a series of non-traditional organometallic Pt(II)-complexes are described. These complexes have a basic [Pt(P<sub>L</sub>)(A<sub>L</sub>)]Cl<sub>2</sub> molecular formula which incorporates either 2-pyrrolidin-2-ylpyridine, 2-(1<i>H</i>-Imidazol-2-yl)pyridine, or 2-(2-pyridyl)benzimidazole as the P<sub>L</sub>; the A<sub>L</sub> is resolved diaminocyclohexane. Precursor [Pt(P<sub>L</sub>)(Cl)<sub>2</sub>] complexes were also characterized for comparison. While the cytotoxicity and DNA binding properties of the three precursors were unexceptional, the corresponding [Pt(P<sub>L</sub>)(A<sub>L</sub>)]<sup>2+</sup> complexes were promising; they exhibited different DNA binding interactions compared with Cisplatin but with similar, if not slightly better, cytotoxicity results. Complexes with 2-pyrrolidin-2-ylpyridine or 2-(2-pyridyl)benzimidazole ligands had similar DNA binding properties to those with 2-(1<i>H</i>-Imidazol-2-yl)pyridine ligands but were not as cytotoxic to all cell lines. The variation in activity between cell lines was remarkable and resulted in significant selectivity indices in MCF10A and MCF-7 breast cancer cell lines, compared with previously described similar Pt(II) complexes such as 56MESS. |
| first_indexed | 2024-03-08T20:43:02Z |
| format | Article |
| id | doaj.art-b8f63d27175a43749bf094451be08f48 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:43:02Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b8f63d27175a43749bf094451be08f482023-12-22T14:13:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241715010.3390/ijms242417150Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer AgentsBrondwyn S. McGhie0Jennette Sakoff1Jayne Gilbert2Christopher P. Gordon3Janice R. Aldrich-Wright4Nanoscale Organisation and Dynamics Group, School of Science, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, AustraliaDepartment of Medical Oncology, Calvary Mater Newcastle Hospital, Waratah, NSW 2298, AustraliaDepartment of Medical Oncology, Calvary Mater Newcastle Hospital, Waratah, NSW 2298, AustraliaNanoscale Organisation and Dynamics Group, School of Science, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, AustraliaNanoscale Organisation and Dynamics Group, School of Science, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, AustraliaCisplatin-type covalent chemotherapeutics are a cornerstone of modern medicinal oncology. However, these drugs remain encumbered with dose-limiting side effects and are susceptible to innate and acquired resistance. The bulk of platinum anticancer research has focused on Cisplatin and its derivatives. Here, we take inspiration from the design of platinum complexes and ligands used successfully with other metals to create six novel complexes. Herein, the synthesis, characterization, DNA binding affinities, and lipophilicity of a series of non-traditional organometallic Pt(II)-complexes are described. These complexes have a basic [Pt(P<sub>L</sub>)(A<sub>L</sub>)]Cl<sub>2</sub> molecular formula which incorporates either 2-pyrrolidin-2-ylpyridine, 2-(1<i>H</i>-Imidazol-2-yl)pyridine, or 2-(2-pyridyl)benzimidazole as the P<sub>L</sub>; the A<sub>L</sub> is resolved diaminocyclohexane. Precursor [Pt(P<sub>L</sub>)(Cl)<sub>2</sub>] complexes were also characterized for comparison. While the cytotoxicity and DNA binding properties of the three precursors were unexceptional, the corresponding [Pt(P<sub>L</sub>)(A<sub>L</sub>)]<sup>2+</sup> complexes were promising; they exhibited different DNA binding interactions compared with Cisplatin but with similar, if not slightly better, cytotoxicity results. Complexes with 2-pyrrolidin-2-ylpyridine or 2-(2-pyridyl)benzimidazole ligands had similar DNA binding properties to those with 2-(1<i>H</i>-Imidazol-2-yl)pyridine ligands but were not as cytotoxic to all cell lines. The variation in activity between cell lines was remarkable and resulted in significant selectivity indices in MCF10A and MCF-7 breast cancer cell lines, compared with previously described similar Pt(II) complexes such as 56MESS.https://www.mdpi.com/1422-0067/24/24/17150anticancer drugsplatinum complexesimidazolepyridine derivatives |
| spellingShingle | Brondwyn S. McGhie Jennette Sakoff Jayne Gilbert Christopher P. Gordon Janice R. Aldrich-Wright Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents International Journal of Molecular Sciences anticancer drugs platinum complexes imidazole pyridine derivatives |
| title | Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents |
| title_full | Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents |
| title_fullStr | Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents |
| title_full_unstemmed | Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents |
| title_short | Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents |
| title_sort | synthesis and characterisation of platinum ii diaminocyclohexane complexes with pyridine derivatives as anticancer agents |
| topic | anticancer drugs platinum complexes imidazole pyridine derivatives |
| url | https://www.mdpi.com/1422-0067/24/24/17150 |
| work_keys_str_mv | AT brondwynsmcghie synthesisandcharacterisationofplatinumiidiaminocyclohexanecomplexeswithpyridinederivativesasanticanceragents AT jennettesakoff synthesisandcharacterisationofplatinumiidiaminocyclohexanecomplexeswithpyridinederivativesasanticanceragents AT jaynegilbert synthesisandcharacterisationofplatinumiidiaminocyclohexanecomplexeswithpyridinederivativesasanticanceragents AT christopherpgordon synthesisandcharacterisationofplatinumiidiaminocyclohexanecomplexeswithpyridinederivativesasanticanceragents AT janiceraldrichwright synthesisandcharacterisationofplatinumiidiaminocyclohexanecomplexeswithpyridinederivativesasanticanceragents |