Cytotoxic homoleptic Ti(iv) compounds of ONO-type ligands: synthesis, structures and anti-cancer activity

Rajesh Manne, Maya Miller, Andrew Duthie, M. Fátima C. Guedes Da Silva*, Edit Y. Tshuva, Tushar S. Basu Baul

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Eight Ti(iv) compounds 1-8, of the type [Ti(L n ) 2 ] where L n is a variously substituted dianionic tridentate acylhydrazone, were synthesized by reacting the appropriate hydrazide with 2-hydroxybenzaldehyde or 2′-hydroxyacetophenone and titanium(iv) tetra(isopropoxide) in a 2 : 2 : 1 molar ratio. The solid-state structures of 1-6 and 7·CH 2 Cl 2 were deduced from the single crystal X-ray diffraction data, which indicated that each L 2− ligand is fully deprotonated and coordinated to the Ti(iv) cation via 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 H 2 L 3 and H 2 L 5 are also reported. All complexes displayed high hydrolytic stability. In vitro 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 5 of this study presents IC 50 values of 2.5 ± 0.2 and 4.2 ± 0.6 μM for ovarian A2780 and colon HT-29 human cancer cells, respectively.

Original languageAmerican English
Pages (from-to)304-314
Number of pages11
JournalDalton Transactions
Volume48
Issue number1
DOIs
StatePublished - 2019

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© The Royal Society of Chemistry.

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