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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Photoactivatable diazido Pt(IV) anticancer complex can bind to and oxidize all four nucleosides
Yiyu Cheng1, Jishuai Zhang, Kui Wu
1Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials; School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China. wukui@wust.edu.cn.
Abstract:
Photoactivatable diazidodihydroxido Pt(iv) complex trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1; py = pyridine) is a promising anticancer agent which can be activated by visible light to induce cancer cell death. DNA has been thought to be involved in the mechanism of action of this kind of Pt(iv) prodrug. However, the detailed photodecomposition pathways of complex 1 and its interaction modes with DNA are complex. Herein we report that upon light irradiation complex 1 can bind to all four nucleosides covalently with the reduced Pt(ii) species. Moreover, apart from the covalent coordination, various oxidation adducts of these four nucleosides induced by the reactive oxidative species (ROS) generated during the photoactivation of the complex 1 have also been identified, especially the induced oxidation of adenosine and cytidine which was firstly reported for this kind of photoactivatable Pt(iv) prodrug. Such dual-action may contribute to the highly potent photo-antiproliferativity of complex 1 towards cancer cells, which may account for the unique mechanism of action of the photoactivatable diazido Pt(iv) anticancer complexes.
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