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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Anti-tumoral Titanium(IV) Complexes Stabilized with Phenolato Ligands and Structure-Activity Relationship

Author(s): Tiankun Zhao*, Peng Wang, Xupeng Zhang, Nan Liu, Wenzhuo Zhao, Yong Zhang, Pengpeng Yuan, Shanjia Li, Mingjun Yang, Zhongduo Yang and Thomas Huhn*

Volume 23, Issue 19, 2023

Published on: 19 May, 2023

Page: [1835 - 1849] Pages: 15

DOI: 10.2174/1568026623666230505104626

Price: $65

Abstract

Titanocene dichloride and budotitane have opened a new chapter in medicinal chemistry of titanium(IV) complexes being novel non-platinum antitumor metallic agents. Numerous efforts have led to the discovery of the diamino bis-phenolato titanium(IV) complexes. Among which, the [ONNO] and [ONON] type ligands namely Salan, Salen and Salalen coordinated titanium(IV) alkoxyl complexes have demonstrated significantly enhanced aqueous stability, their in vitro and in vivo antitumor efficacy, mechanism of action, structure-activity relationships and combined tumor therapy have been intensively investigated. Replacement of the labile alkoxyls with a second chelator resulted in structural rigid titanium(IV) complexes, which showed exceedingly good aqueous stability and potent antitumor activity both in vitro and in vivo. The unique ligand system successfully allowed the access of isotopic [45Ti]Titanium(IV) complexes, post-synthetic modification, facile synthetic protocols and antitumor congeneric zirconium(IV) and hafnium(IV) complexes. This review presents recent research progress in the field of antitumor group 4 metal complexes stabilized with phenolato ligands; especially their structure-activity relationships are summarized.

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