Coordination complexes of titanium(IV) for anticancer therapy

Edit Y. Tshuva*, Maya Miller

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

12 Scopus citations

Abstract

Titanium(IV) coordination complexes represent attractive alternatives to platinum-based anticancer drugs. The advantage of the titanium metal lies in its low toxicity, and the hydrolysis of titanium(IV) coordination complexes in biological water-based environment to the safe and inert titanium dioxide is an enormous benefit. On the other hand, the rapid hydrolysis of titanium(IV) complexes in biological environment and their rich aquatic chemistry hampered the exploration and the development of effective compounds. Titanium(IV) complexes were the first to enter clinical trials for cancer treatment following the success of platinum-based chemotherapy, with the pioneering compounds titanocene dichloride and budotitane. Despite the high efficacy and low toxicity observed in vivo, the compounds failed the trials due to insufficient efficacy to toxicity ratio and formulation complications. The rapid hydrolysis of the complexes led to formation of multiple undefined aggregates and difficulties in isolating and identifying the particular active species and its precise cellular target. Numerous derivatives with different labile ligands or substitutions on the inert ones contributed to improve the complex anticancer features, and the best ones were comparable with, and occasionally better than cisplatin. Hydrolytic stability was improved in some cases but remained challenging. The following generation of phenolato-based complexes that came three decades later exhibited high activity and markedly improved stability, where no dissociation was observed for weeks in biological solutions. Complexes of no labile ligands whatsoever that remain intact in solution demonstrated in vitro and in vivo efficacy, with no signs of toxicity to the treated animals. Mechanistic insights gained for the different complexes analyzed include, among others, possible interaction with DNA and induction of apoptosis. Such complexes are highly promising for future exploration and clinical development.

Original languageAmerican English
Title of host publicationMetal Ions in Life Sciences
PublisherDe Gruyter Open Ltd.
Pages219-250
Number of pages32
DOIs
StatePublished - 2018

Publication series

NameMetal Ions in Life Sciences
Volume18
ISSN (Print)1559-0836
ISSN (Electronic)2041-9821

Bibliographical note

Publisher Copyright:
© 2018 De Gruyter. All rights reserved.

Keywords

  • Anticancer
  • Cytotoxicity
  • Metallodrugs
  • Non-platinum
  • Titanium(IV)

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