Publication
Vanadium(V) Pyridine‐Containing Schiff Base Catecholate Complexes are Lipophilic, Redox‐Active and Selectively Cytotoxic in Glioblastoma (T98G) Cells
Publisher:
Wiley
Date:
24-10-2023
DOI:
10.1002/CHEM.202302271
Abstract: Two new series of complexes with pyridine‐containing Schiff bases, [VVO(SALIEP)L] and [VVO(Cl‐SALIEP)L] (SALIEP = N‐(salicylideneaminato)‐2‐(2‐aminoethylpyridine Cl‐SALIEP = N‐(5‐chlorosalicylideneaminato)‐2‐(2‐aminoethylpyridine, L = catecholato(2‐) ligand) were synthesized. Characterization by 1H and 51V NMR and UV‐Vis spectroscopies confirmed that: 1) most complexes form two major geometric isomers in solution, and [VVO(SALIEP)(DTB)] (DTB = di‐tert‐butylcatecholato(2‐)) forms two isomers that equilibrate in solution and 2) tert‐butyl substituents was necessary to stabilize the reduced V(IV) species (EPR spectroscopy and cyclic voltammetry). The pyridine moiety within the Schiff base ligands significantly changed their chemical properties with unsubstituted catecholate ligands compared with the parent HSHED (N‐(salicylideneaminato)‐Nˊ‐(2‐hydroxyethyl)‐1,2‐ethanediamine) Schiff base complexes. Immediate reduction to V(IV) occurred for the unsubstituted‐catecholato V(V) complexes on dissolution in DMSO. By contrast, the pyridine moiety within the Schiff base significantly improved the hydrolytic stability of [VVO(SALIEP)(DTB)] compared with [VVO(HSHED)(DTB)]. [VVO(SALIEP)(DTB)] had moderate stability in cell culture media. There was significant cellular uptake of the intact complex by T98g (human glioblastoma) cells and very good anti‐proliferative activity (IC50 6.7 ± 0.9 μM, 72 h), which was ~five‐fold higher compared with the non‐cancerous human cell line, HFF‐1 (IC50 34 ± 10 μM). This made it a potential drug candidate for the treatment of advanced gliomas by intracranial injections.