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A dinuclear monofunctional platinum(II) complex with an aromatic linker shows low reactivity towards glutathione but high DNA binding ability and antitumor activity

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Abstract

Multinuclear Pt(II) complexes represent a novel class of antitumor agents. In this work, a dinuclear monofunctional Pt(II) complex {[cis-Pt(NH3)2Cl]2(4,4′-methylenedianiline)}(NO3)2 (1) was synthesized and characterized by 1H NMR, electrospray mass spectrometry, and elemental analysis. The 2D [1H,15N] heteronuclear single quantum coherence NMR spectra of 15N-labeled 1 revealed that the cationic core of this water-soluble complex hardly hydrolyzes in aqueous solution and reacts very slowly with glutathione. Hydrolysis appears not to be an essential step for the formation of Pt–guanosine-5′-monophosphate (5′-GMP) or Pt–DNA adducts because the complex can react readily with 5′-GMP and partially transform B-DNA into its Z form. Such properties are desired to achieve the goal of enhancing cytotoxicity and lowering side effects of Pt(II) complexes. In fact, complex 1 is highly cytotoxic against the murine leukemia (P-388) and the human non-small-cell lung cancer (A-549) cell lines, and it is more cytotoxic than cisplatin at most concentrations tested.

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Acknowledgements

Financial support from the National Natural Science Foundation of China (nos. 20231010, 20228102, 30370351) and the Natural Science Foundation of Jiangsu Province (no. BK 2005209) is gratefully acknowledged.

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Authors and Affiliations

  1. State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, People’s Republic of China

    Damin Fan, Xiaoliang Yang, Shouchun Zhang, Jiafei Mao & Zijian Guo

  2. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, 210093, People’s Republic of China

    Xiaoyong Wang

  3. State Key Laboratory for New Drug Research, Shanghai Institute of Materia Medica, Shanghai, 200031, People’s Republic of China

    Jian Ding & Liping Lin

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  1. Damin Fan
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  2. Xiaoliang Yang
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Correspondence to Xiaoyong Wang or Zijian Guo.

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Fan, D., Yang, X., Wang, X. et al. A dinuclear monofunctional platinum(II) complex with an aromatic linker shows low reactivity towards glutathione but high DNA binding ability and antitumor activity. J Biol Inorg Chem 12, 655–665 (2007). https://doi.org/10.1007/s00775-007-0214-1

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