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Reacting variously substituted dianionic tridentate ONO-type acylhydrazone ligands with titanium( ) tetra(isopropoxide) gave a new class of eight homoleptic titanium( ) compounds showing exceptional stability and promising cytotoxicity., Eight Ti( ) compounds , of the type [Ti(L ) ] where L is a variously substituted dianionic tridentate acylhydrazone, were synthesized by reacting the appropriate hydrazide with 2-hydroxybenzaldehyde or 2′-hydroxyacetophenone and titanium( ) tetra(isopropoxide) in a 2 : 2 : 1 molar ratio. The solid-state structures of and ·CH Cl were deduced from the single crystal X-ray diffraction data, which indicated that each L ligand is fully deprotonated and coordinated to the Ti( ) cation the enolic oxygen, the imino nitrogen and the phenolic oxygen atoms (ONO donor set) in an enol tautomeric form, the metal assuming the distorted octahedral geometry. The structures of pro-ligands and are also reported. All complexes displayed high hydrolytic stability. cytotoxicity assays towards human ovarian A2780 and colon HT-29 cancer cell lines revealed the activity dependence on the acylhydrazone substituents, with electron-donating groups on the phenolato units enhancing the solubility and promoting cytotoxicity. The lead compound of this study presents IC values of 2.5 ± 0.2 and 4.2 ± 0.6 μM for ovarian A2780 and colon HT-29 human cancer cells, respectively.

Racemic and optically pure tetrakis(phenolato) Ti(iv) complex exhibit high hydrolytic stability and similar cytotoxicity for both enantiomers. Higher activity of the racemate on drug-resistant lines implies a beneficial activity of both isomers., A tetrakis(phenolato) Ti(iv) complex was synthesized in racemic and optically pure form, exhibiting high hydrolytic stability, and similar cytotoxicity for all stereochemical forms on HT-29 and A2780 cancer cells. Higher activity of the racemate on drug-resistant A2780cp and A2780adr lines implies a beneficial activity of both enantiomers rendering enantiomeric resolution unnecessary.

Vanadium complexes are attractive candidates for anticancer chemotherapy, although often suffering from rich aqueous chemistry and hydrolytic instability. We have introduced an LVO family of vanadium oxo complexes, L being a diaminotris(phenolato) chlelating ligand, demonstrating high hydrolytic stability in water along with promising in vitro and in vivo efficacy. Herein we analyzed mechanistic aspects of the reactivity of such complexes in cellular environment. A representative complex exhibited high activity toward all lines in the NIH NCI-60 panel, with an average GI50 value of 0.7 ± 0.5 μM, and with a unique reactivity pattern implying a distinct mechanism. Free ligands demonstrated cytotoxicity similar to that of their vanadium complexes, were identified in cells treated with the complex, and induced apoptosis as did the parent complex, all implying their participation as active species. Cell cycle studies pointed to possible arrest mostly at the S phase, with some variations for the complex and ligand on the two lines analyzed. Nevertheless, the vanadium ion apparently accelerated cellular entry, as the activity was evident following markedly shorter periods of incubation with the extracellular complex when compared with the free ligand. The results displayed herein overall highlight the role of the vanadium complex as a pro-drug.