Dalton Transactions
Paper
Conclusions
Notes and references
In this study, we present new Pt(IV) derivatives of cisplatin
bearing valproic acid and cinnamic acid as axial ligands.
These Pt(IV) complexes were designed to prepare prospective
multi-action Pt-based drugs efficiently for killing tumour cells.
The in vitro biological assay demonstrated the superior anti-
proliferative activity of these Pt(IV) derivatives against a panel
of cancer cell lines of various origins, particularly in the case
of the Cin-Pt(IV)-Val complex, which exhibited antiproliferative
activity at sub-micromolar concentrations. The Cin-Pt(IV)-Val
complex was confirmed to cause tumour cell arrest at the G2/
M phase of the cell cycle, and specifically inhibit the HDAC
and MMP-2 and -9 activities as well as increase lipophilicity
that enhances cellular accumulation. In vivo, the Cin-Pt(IV)-Val
complex significantly inhibited tumour growth and efficiently
overcame serious kidney injuries of CDDP. These results
obtained in this study also supported the hypothesis that the
investigated Cin-Pt(IV)-Val complex, upon entering the cancer
cells, was reduced by intracellular reductants, thereby releas-
ing the DNA-damaging Pt(II) moiety along with biologically
active and synergistic acting ligands and exemplified the mode
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Author contributions
Conceptualization: Yang Li, Shan Shi, Wei Li. Data curation:
Yang Li and Shan Shi. Formal analysis: Xudong Zhao and 15 Q. Q. Cheng, H. D. Shi, H. X. Wang, Y. Z. Min, J. Wang and
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Shurong Zhang, Xin Wang, and Yijian Zhu. Methodology: 16 Y. L. Chen, S. T. Huang, F. M. Sun, Y. L. Chiang,
Yang Li, Shan Shi, and Xin Wang. Project administration:
Wei Li. Resources: Xudong Zhao, Shurong Zhang, and Wei Li.
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Conflicts of interest
The authors declare no conflict of interest.
Acknowledgements
This work was supported by the Chongqing Municipality 23 Y. Huang, F. Zeng, L. Xu, J. Zhou, X. Liu and H. Le, Oncol.
Education Commission (KJ1400212), the Municipal Res., 2013, 20, 499–507.
Science and Technology Committee of Chongqing 24 R. K. Pathak, S. Marrache, J. H. Choi, T. B. Berding and
(CSTC2014jcyjA0019), and the School of Pharmacy, Chongqing
Medical University.
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Dalton Trans., 2021, 50, 11180–11188 | 11187