1. Synthesis, in vitro antitumor evaluation and structure activity relationship of heptacoordinated amino-bis(Phenolato) Ti(IV) complexes stabilized by 2,6-dipicolinic acid.
- Author
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Li S, Zhang X, Zhao T, Liu N, Zhang Y, Wang P, Yang Z, and Huhn T
- Subjects
- Humans, Structure-Activity Relationship, HeLa Cells, Apoptosis drug effects, Molecular Structure, Cell Proliferation drug effects, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Picolinic Acids chemistry, Picolinic Acids pharmacology, Picolinic Acids chemical synthesis, Coordination Complexes chemistry, Coordination Complexes pharmacology, Coordination Complexes chemical synthesis, Titanium chemistry, Titanium pharmacology, Drug Screening Assays, Antitumor
- Abstract
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
1 H and13 C-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., (© 2024. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)- Published
- 2024
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