Anti-tumoral Titanium Complexes Stabilized with Phenolato Ligands and Structure-Activity Relationship.

Titanocene dichloride and budotitane have opened a new chapter in medicinal chemistry of titanium complexes being novel non-platinum antitumor metallic agents. Numerous efforts have led to the discovery of the diamino -phenolato titanium complexes. Among which, the [ONNO] and [ONON] type ligands namely Salan, Salen and Salalen coordinated titanium alkoxyl complexes have demonstrated significantly enhanced aqueous stability, their and 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 complexes, which showed exceedingly good aqueous stability and potent antitumor activity both and . The unique ligand system successfully allowed the access of isotopic [Ti]Titanium complexes, post-synthetic modification, facile synthetic protocols and antitumor congeneric zirconium and hafnium 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.