title: Trans titanium(IV) complexes of salen ligands exhibit high antitumor activity.
abstract: Salen-titanium(IV) complexes are introduced as a new family of highly efficient antitumor complexes, being the first cytotoxic titanium(IV) complexes of trans labile ligands, as characterized crystallographically. Four complexes with different aromatic substitutions were analyzed, reveling a meaningful effect of the ligand structure on the complex performance. All complexes exhibit high hydrolytic stability, where the labile OAr ligands hydrolyze in a 10% D(2)O solution with t(1/2) ranging from 2 to 11 h. The IC(50) values obtained for three of the salen complexes studied on HT-29 colon and OVCAR-1 ovarian cells demonstrate activity that exceeds those of the known tianium(IV) complexes Cp(2)TiCl(2) and (bzac)(2)Ti(OiPr)(2) and that of cisplatin, where the most active para-chlorinated complex exhibits activity enhancement relative to cisplatin by 10-fold.
authors.affiliation: The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Avia
authors.initials: A
authors.lastname: Tzubery
authors.forename: Edit Y
authors.initials: EY
authors.lastname: Tshuva
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005029:Ethylenediamines / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014025:Titanium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D005029:Ethylenediamines; D008024:Ligands; D009942:Organometallic Compounds; C011452:disalicylaldehyde ethylenediamine; D014025:Titanium