Ionic Liquids Based on Valproate as Antitumor Agents Against Human Neuroblastoma

Ionic liquids (ILs) containing active pharmaceutical ingredients (APIs) have been reported as a successful approach to improve drug delivery and to overcome other drawbacks of pharmaceutical industry. Moreover, ILs-API derived from antibiotics revealed antimicrobial activity against sensitive bacteria and, particularly, increased for resistant species. The higher antimicrobial activity can be attributed to the improved drug delivery and solubility, but also to some specific interactions. On the other hand, the search for alternative and effective therapies to fight cancer pointed out ionic liquids as potential therapeutic agents with antitumor properties. In this context, several ILs with valproate (VPA) as API were synthesized and studied in terms of their bioactivity against neuroblastoma. The toxicity of the prepared ionic liquids was evaluated by MTT cell metabolic assay in human neuroblastoma SH-SY5Y and human primary Gingival Fibroblast (GF) cell lines, in which they showed inhibitory effects. Low cytotoxicity against GF cell lines was also observed, suggesting that these compounds are not toxic to human cell lines. 1-(2-hydroxyethyl)-2,3-dimethylimidazolium 2-propylpentanoate, [C₂OHDMiM][VPA], demonstrated an outstanding antitumor activity against SH-SY5Y and lower activity against the non-neoplastic GF line. The herein assessed compounds played an important role in the modulation of the signaling pathways involved in the cellular behavior. This work also highlights the potential of these ILs-API as possible antitumor agents.