1. An Axially CBD‐Containing Novel Pt(IV) Prodrug Designed to Synergistically Enhance Antitumor Activity by Inducing Mitochondrial Dysfunction.
- Author
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Wang, Ling, Lu, Zhiping, Shi, Pengmin, Peng, Yusheng, Yang, Jing, Liao, Xiali, Yang, Bo, and Gaoa, Chuanzhu
- Abstract
ABSTRACT In recent years, significant attention has been given to the strategy of linking novel active molecules with different biological targets and antitumor mechanisms to the axial positions of Pt(IV) complexes, aiming to synthesize new Pt(IV) antitumor complexes with excellent properties. In this study, Satraplatin analogs and the highly lipophilic bioactive molecule cannabidiol (CBD) were chosen as the main research subjects. By combining these two and introducing other bioactive small molecules, we aimed to enrich the functionalities of Pt(IV) antitumor complexes. Five new multifunctional Pt(IV) antitumor complexes, P1–P5, were prepared. All Pt(IV) prodrugs demonstrated antitumor effects in various tumor cell lines. Notably, compound P1 exhibited significant inhibitory effects, with half‐maximal inhibitory concentration (IC50) values that were 2.1, 1.5, and 1.3 times higher than those of satraplatin in HCT‐116, A549, and HeLa cell lines, respectively, and 2.4, 1.5, and 2.0 times higher than those of the combination of satraplatin and CBD. The cytotoxicity of P1 toward cancer cell lines is significantly higher than that of the combination therapy group, providing preliminary evidence that the strategy of combining CBD and platinum‐based antitumor drugs into a complex is highly effective in simultaneously enhancing the cytotoxicity of both, resulting in a good synergistic antitumor effect. Further research shows that after treating cells with P1, the induced ROS generation increases in a dose‐dependent manner, disrupting the cell's redox homeostasis, leading to oxidative stress, and ultimately causing cell apoptosis. This strategy of introducing the bioactive molecule CBD into platinum‐based drug formation complexes to improve efficacy has been shown to be feasible and deserves further study. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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