Synthesis, in vitro antitumor evaluation and structure activity relationship of heptacoordinated amino-bis(Phenolato) Ti(IV) complexes stabilized by 2,6-dipicolinic acid

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2024
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Li, Shanjia
Zhang, Xupeng
Liu, Nan
Zhang, Yong
Wang, Peng
Yang, Zhongduo
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Journal of Biological Inorganic Chemistry (JBIC). Springer. 2024, 29(3), pp. 315-330. ISSN 0949-8257. eISSN 1432-1327. Available under: doi: 10.1007/s00775-024-02059-9
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Eighteen novel Ti(IV) complexes stabilized by different chelating amino-bis(phenolato) (ONNO, ONON, ONOO) ligands and 2,6-dipicolinic acid as a second chelator were synthesized with isolated yields ranging from 79 to 93%. Complexes were characterized by 1H and 13C-NMR spectroscopy, as well as by HRMS and X-Ray diffraction analysis. The good to excellent aqueous stability of these Ti(IV) complexes can be modulated by the substitutions on the 2-position of the phenolato ligands. Most of the synthesized Ti(IV) complexes demonstrated potent inhibitory activity against Hela S3 and Hep G2 tumor cells. Among them, the naphthalenyl based Salan type 2j, 2-picolylamine based [ONON] type 2n and N-(2-hydroxyethyl) based [ONOO] type 2p demonstrated up to 40 folds enhanced cytotoxicity compared to cisplatin together with a significantly reduced activity against healthy AML12 cells. The three Ti(IV) complexes exhibited fast cellular uptake by Hela S3 cells and induced almost exclusively apoptosis. 2j could trigger higher level of ROS generation than 2p and 2n.

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ISO 690LI, Shanjia, Xupeng ZHANG, Tiankun ZHAO, Nan LIU, Yong ZHANG, Peng WANG, Zhongduo YANG, Thomas HUHN, 2024. Synthesis, in vitro antitumor evaluation and structure activity relationship of heptacoordinated amino-bis(Phenolato) Ti(IV) complexes stabilized by 2,6-dipicolinic acid. In: Journal of Biological Inorganic Chemistry (JBIC). Springer. 2024, 29(3), pp. 315-330. ISSN 0949-8257. eISSN 1432-1327. Available under: doi: 10.1007/s00775-024-02059-9
BibTex
@article{Li2024Synth-70067,
  year={2024},
  doi={10.1007/s00775-024-02059-9},
  title={Synthesis, in vitro antitumor evaluation and structure activity relationship of heptacoordinated amino-bis(Phenolato) Ti(IV) complexes stabilized by 2,6-dipicolinic acid},
  number={3},
  volume={29},
  issn={0949-8257},
  journal={Journal of Biological Inorganic Chemistry (JBIC)},
  pages={315--330},
  author={Li, Shanjia and Zhang, Xupeng and Zhao, Tiankun and Liu, Nan and Zhang, Yong and Wang, Peng and Yang, Zhongduo and Huhn, Thomas}
}
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