Issue 32, 2021

ctc-[Pt(NH3)2(cinnamate)(valproate)Cl2] is a highly potent and low-toxic triple action anticancer prodrug

Abstract

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.

Graphical abstract: ctc-[Pt(NH3)2(cinnamate)(valproate)Cl2] is a highly potent and low-toxic triple action anticancer prodrug

Supplementary files

Article information

Article type
Paper
Submitted
29 Apr 2021
Accepted
12 Jul 2021
First published
12 Jul 2021

Dalton Trans., 2021,50, 11180-11188

ctc-[Pt(NH3)2(cinnamate)(valproate)Cl2] is a highly potent and low-toxic triple action anticancer prodrug

Y. Li, S. Shi, S. Zhang, Z. Gan, X. Wang, X. Zhao, Y. Zhu, M. Cao, X. Wang and W. Li, Dalton Trans., 2021, 50, 11180 DOI: 10.1039/D1DT01421H

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