Synthesis and Anticancer Activity of Bis(2-picolyl)amine Derivatives with a Biaryl Moiety as a Photosensitizer
Metal complexes have potential applications in drug discovery due to their unique properties. For example, zinc(II) ions (Zn<sup>II</sup>) exhibit a high affinity for DNA and have been used as active centers in artificial protein/small-molecule metallonucleases. In this study, we designe...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Chemistry |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2624-8549/7/2/41 |
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| Summary: | Metal complexes have potential applications in drug discovery due to their unique properties. For example, zinc(II) ions (Zn<sup>II</sup>) exhibit a high affinity for DNA and have been used as active centers in artificial protein/small-molecule metallonucleases. In this study, we designed a series of ligands containing a biaryl moiety as a photosensitizer to synthesize Zn<sup>II</sup> complexes with enhanced DNA affinity for use as DNA photocleavage reagents. The DNA photocleavage activity of these complexes was evaluated using the pUC19 plasmid, revealing that the Zn<sup>II</sup> complex bearing the 4′-biphenyl-bpa (bpa = bis(2-picolyl)amine) ligand <b>L1</b> exhibited the strongest DNA photocleavage activity. Further analysis of the biological activity of the Zn<sup>II</sup> complex of <b>L1</b> in the human pancreatic cancer cell line MIA PaCa-II demonstrated that its cytotoxic activity increased in a UV irradiation time-dependent manner, with an IC<sub>50</sub> value of 14.2 μM. Fluorescence staining revealed that the Zn<sup>II</sup> complex of <b>L1</b> generates reactive oxygen species in cells, leading to DNA double-strand breaks upon UV irradiation and ultimately resulting in necrotic cell death. These findings highlight the potential of the Zn<sup>II</sup> complex of <b>L1</b> as a photochemotherapeutic agent for pancreatic cancer. |
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| ISSN: | 2624-8549 |