Deakin University
Browse

File(s) under permanent embargo

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

journal contribution
posted on 2019-01-07, 00:00 authored by Rajesh Manne, Maya Miller, Andrew DuthieAndrew Duthie, M Fátima C Guedes da Silva, Edit Y Tshuva, Tushar S Basu Baul
Eight Ti(iv) compounds 1-8, of the type [Ti(Ln)2] where Ln 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·CH2Cl2 were deduced from the single crystal X-ray diffraction data, which indicated that each L2- 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 H2L3 and H2L5 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 IC50 values of 2.5 ± 0.2 and 4.2 ± 0.6 μM for ovarian A2780 and colon HT-29 human cancer cells, respectively.

History

Journal

Dalton transactions

Volume

48

Pagination

304-314

Location

Cambridge, Eng.

eISSN

1477-9234

Language

eng

Publication classification

C Journal article, C1 Refereed article in a scholarly journal

Copyright notice

2019, The Royal Society of Chemistry

Issue

1

Publisher

Royal Society of Chemistry