Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties
Herein is described the development of a series of novel quadruplex DNA (QDNA)-stabilising cyclometallated square–planar metal complexes (CMCs). Melting experiments using quadruplex DNA (QDNA) demonstrated that interactions with the complexes increased the melting temperature by up to 19 °C. This QD...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10469 |
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| 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 | Herein is described the development of a series of novel quadruplex DNA (QDNA)-stabilising cyclometallated square–planar metal complexes (CMCs). Melting experiments using quadruplex DNA (QDNA) demonstrated that interactions with the complexes increased the melting temperature by up to 19 °C. This QDNA stabilisation was determined in two of the major G-quadruplex structures formed in the human c-MYC promoter gene (c-MYC) and a human telomeric repeat sequence (H-Telo). The CMCs were found to stabilise H-telo more strongly than c-MYC, and the CMCs with the highest cytotoxic effect had a low–moderate correlation between H-telo binding capacity and cytotoxicity (R<sup>2</sup> values up to 10 times those of c-MYC). The melting experiments further revealed that the stabilisation effect was altered depending on whether the CMC was introduced before or after the formation of QDNA. All CMCs’ GI<sub>50</sub> values were comparable or better than cisplatin in human cancer cell lines HT29, U87, MCF-7, H460, A431, Du145, BE2-C, SJ-G2, MIA, and ADDP. Complexes <b>6</b>, <b>7,</b> and <b>9</b> were significantly more cytotoxic than cisplatin in all cell lines tested and had good to moderate selectivity indices, 1.7–4.5 in MCF10A/MCF-7. The emission quantum yields were determined to be relatively high (up to 0.064), and emission occurred outside cellular autofluorescence, meaning CMC fluorescence is ideal for in vitro analyses. |
| first_indexed | 2024-03-09T23:47:06Z |
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| language | English |
| last_indexed | 2024-03-09T23:47:06Z |
| publishDate | 2022-09-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c822f045373d48459466dc4ea1eff1c22023-11-23T16:42:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181046910.3390/ijms231810469Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent PropertiesBrondwyn S. McGhie0Jennette Sakoff1Jayne Gilbert2Christopher P. Gordon3Janice R. Aldrich-Wright4School of Science, Western Sydney University, Locked Bag 1797 Penrith South DC, Penrith, NSW 2751, AustraliaCalvary Mater Newcastle, Waratah, Newcastle, NSW 2298, AustraliaCalvary Mater Newcastle, Waratah, Newcastle, NSW 2298, AustraliaSchool of Science, Western Sydney University, Locked Bag 1797 Penrith South DC, Penrith, NSW 2751, AustraliaSchool of Science, Western Sydney University, Locked Bag 1797 Penrith South DC, Penrith, NSW 2751, AustraliaHerein is described the development of a series of novel quadruplex DNA (QDNA)-stabilising cyclometallated square–planar metal complexes (CMCs). Melting experiments using quadruplex DNA (QDNA) demonstrated that interactions with the complexes increased the melting temperature by up to 19 °C. This QDNA stabilisation was determined in two of the major G-quadruplex structures formed in the human c-MYC promoter gene (c-MYC) and a human telomeric repeat sequence (H-Telo). The CMCs were found to stabilise H-telo more strongly than c-MYC, and the CMCs with the highest cytotoxic effect had a low–moderate correlation between H-telo binding capacity and cytotoxicity (R<sup>2</sup> values up to 10 times those of c-MYC). The melting experiments further revealed that the stabilisation effect was altered depending on whether the CMC was introduced before or after the formation of QDNA. All CMCs’ GI<sub>50</sub> values were comparable or better than cisplatin in human cancer cell lines HT29, U87, MCF-7, H460, A431, Du145, BE2-C, SJ-G2, MIA, and ADDP. Complexes <b>6</b>, <b>7,</b> and <b>9</b> were significantly more cytotoxic than cisplatin in all cell lines tested and had good to moderate selectivity indices, 1.7–4.5 in MCF10A/MCF-7. The emission quantum yields were determined to be relatively high (up to 0.064), and emission occurred outside cellular autofluorescence, meaning CMC fluorescence is ideal for in vitro analyses.https://www.mdpi.com/1422-0067/23/18/10469cyclometallatedG-quadruplexPt(II)anticancer |
| spellingShingle | Brondwyn S. McGhie Jennette Sakoff Jayne Gilbert Christopher P. Gordon Janice R. Aldrich-Wright Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties International Journal of Molecular Sciences cyclometallated G-quadruplex Pt(II) anticancer |
| title | Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties |
| title_full | Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties |
| title_fullStr | Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties |
| title_full_unstemmed | Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties |
| title_short | Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties |
| title_sort | novel planar pt ii cyclometallated cytotoxic complexes with g quadruplex stabilisation and luminescent properties |
| topic | cyclometallated G-quadruplex Pt(II) anticancer |
| url | https://www.mdpi.com/1422-0067/23/18/10469 |
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