Phenolato Ti(iv) hexacoordinate complexes for anticancer chemotherapy: enhancement of solubility, hydrolytic stability, and cytotoxicity

Mohammad Taha, Edit Y. Tshuva*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

A new series of five titanium(iv) complexes based on diaminobis(phenolato)-bis(alkoxo) ligands with different substitutions was synthesized and characterized. All complexes were analyzed by X-ray crystallography, and all structures indicated C2 symmetrical octahedral compounds. All complexes exhibited enhanced solubility in aqueous media compared with the parent methylated derivative phenolaTi (up to 0.4 vs. 0.05 mg ml−1 of phenolaTi) due to halogen and alkoxo/hydroxo substitutions, with particularly enhanced water solubility for the methoxylated and hydroxylated derivatives. In particular, high hydrolytic stability was recorded for all derivatives, with the t½ for ligand hydrolysis of more than 8 days, as established by 1H NMR and HR-MS. All complexes were cytotoxic toward human ovarian A2780, colon HT-29, and cervical HeLa cancer cell lines (IC50 values in the range of 0.3-40 μM), with negligible activity toward non-cancerous MRC-5 cells. The halogenated compounds of this series exhibit the best combination of stability and activity, making them highly promising for anticancer applications.

Original languageEnglish
Pages (from-to)7664-7672
Number of pages9
JournalDalton Transactions
Volume52
Issue number22
DOIs
StatePublished - 3 May 2023

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© 2023 The Royal Society of Chemistry.

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