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Updated: Jul 30, 2025
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and Characterisation of Fluorescent Novel Pt(II) Cyclometallated Complexes with Anticancer Activity
Brondwyn S McGhie1, Jennette Sakoff2, Jayne Gilbert2
1School of Science, Nanoscale Organisation and Dynamics Group, Western Sydney University, Locked Bag 1797 Penrith South DC, Penrith, NSW 2751, Australia.
Abstract:
Cancer poses a significant threat to global health and new treatments are required to improve the prognosis for patients. Previously, unconventional platinum complexes designed to incorporate polypyridyl ligands paired with diaminocyclohexane have demonstrated anticancer activity in KRAS mutated cells, previously thought to be undruggable and have cytotoxicity values up to 100 times better than cisplatin. In this work, these complexes were used as inspiration to design six novel cyclometallated examples, whose fluorescence could be exploited to better understand the mechanism of action of these kinds of platinum drugs. The cytotoxicity results revealed that these cyclometallated complexes (CMCs) have significantly different activity compared to the complexes that inspired them; they are as cytotoxic as cisplatin and have much higher selectivity indices in breast cancer cell lines (MCF10A/MCF-7). Complexes 1b, 2a, and 3b all had very high selectivity indexes compared to previous Pt(II) complexes. This prompted further investigation into their DNA binding properties, which revealed that they had good affinity to ctDNA, especially CMCs 1a and 3b. Their inherent fluorescence was successfully utilised in the calculation of their DNA binding affinity and could be useful in future work.
Insights
Novel platinum complexes show potent anticancer activity and high selectivity in breast cancer cells. Their fluorescence aids in understanding DNA binding, offering new therapeutic strategies for cancer treatment.
Area of Science:
- Medicinal Chemistry
- Inorganic Chemistry
- Cancer Research
Background:
- Cancer remains a major global health challenge requiring novel therapeutic agents.
- Previous platinum complexes with polypyridyl ligands showed promise against KRAS-mutated cancers.
- Diaminocyclohexane-based platinum complexes offer improved cytotoxicity over cisplatin.
Purpose of the Study:
- To design and synthesize novel fluorescent cyclometallated platinum complexes (CMCs).
- To evaluate the cytotoxicity and selectivity of these CMCs in breast cancer cell lines.
- To investigate the DNA binding properties and mechanism of action of promising CMCs.
Main Methods:
- Synthesis of six novel cyclometallated platinum complexes.
- Cytotoxicity assays using breast cancer cell lines (MCF10A/MCF-7).
- DNA binding studies using ctDNA and fluorescence spectroscopy.
Main Results:
- CMCs exhibit comparable cytotoxicity to cisplatin but with significantly higher selectivity indices.
- Complexes 1b, 2a, and 3b demonstrated excellent selectivity.
- CMCs 1a and 3b showed good affinity for ctDNA, with fluorescence enabling binding affinity calculation.
Conclusions:
- Novel CMCs present a promising new class of platinum-based anticancer agents.
- Their inherent fluorescence is a valuable tool for mechanistic studies and drug development.
- These CMCs offer potential for improved breast cancer treatment with enhanced selectivity.
