Synthesis, chemical characterization and DNA interaction study of a new valproate zinc (II) ternary complex

Valproic acid (Valp) is an antiepileptic drug (AED) that has the broad spectrum across all types of seizures and epileptic syndromes. Some metal ions like zinc has been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and research. Zinc{ll) complexes are stabilized with N-donor ligands. In this context, nicotinamide (Nic) is an important biological N-donor ligand present in metabolic process of mammalian organisms. Furthermore, that molecule has been shown to exert a number of anti-inflammatory and redox properties. In this way, was synthetized a new ternary complex with zinc and nicotinamide (complex 2) as a new anticonvulsant prototype. 1HNMR and 13CNMR spectra have shown the stoichiometric ratio of the chemical reaction is 2 : 2 : 1 (Valp : Nic: Zn(ll)). Therefore, crystallographic data have confirm this structure is a ternary structure in the solid state. The acute cytotoxicity test (24 h) of complex 2 against Artemia saline presented low toxicity compared to the starting material (sodium valproate). In other hand, Plasmidial DNA interaction assay (single and double DNA breaks analysis by electrophoresis) and CT -DNA interaction assay (double helix interaction type by circular dichroism spectrophotometry) have shown complex 2 has low genotoxic activity, when compared to the nicotinamide control trial, indicating that this ternary complex has potential application in the development of a new drug. Acknowledgment to FAPERGS- PRONUPEQ, Grant/Award Number: 16/2551-0000523-0.