- Ctc-[Pt(NH3)2(cinnamate)(valproate)Cl2] is a highly potent and low-toxic triple action anticancer prodrug
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Pt(iv) prodrugs have gained tremendous attention due to their indisputable advantages compared to cisplatin. Herein, new Pt(iv) derivatives with cinnamic acid at the first axial position, and inhibitor of matrix metalloproteinases-2 and-9, histone deacetylase, cyclooxygenase or pyruvate dehydrogenase at the second axial position are constructed to develop multi-action prodrugs. We demonstrate that Pt(iv) prodrugs are reducible and have superior antiproliferative activity with IC50 values at submicromolar concentrations. Notably, Pt(iv) prodrugs exhibit highly potent anti-tumour activity in an in vivo breast cancer model. Our results support the view that a triple-action Pt(iv) prodrug acts via a synergistic mechanism, which involves the effects of CDDP and the effects of axial moieties, thus jointly leading to the death of tumour cells. These findings provide a practical strategy for the rational design of more effective Pt(iv) prodrugs to efficiently kill tumour cells by enhancing their cellular accumulation and tuning their canonical mechanism.
- Li, Yang,Shi, Shan,Zhang, Shurong,Gan, Zongjie,Wang, Xin,Zhao, Xudong,Zhu, Yijian,Cao, Meiting,Wang, Xiaoyue,Li, Wei
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supporting information
p. 11180 - 11188
(2021/08/25)
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- Hydroxy protection groups
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The present invention concerns a method for preparing unprotected hydroxy compounds or acylated derivatives thereof by conversion of silyl alkyl-protected hydroxy compounds. The invention also relates to novel intermediates useful in the method and for other purposes.
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