A versatile salicyl hydrazonic ligand and its metal complexes as antiviral agents

• Published in: Journal of inorganic biochemistry Vol. 150; pp. 9 - 17
• Main Authors: Rogolino, D., Carcelli, M., Bacchi, A., Compari, C., Contardi, Laura, Fisicaro, E., Gatti, A., Sechi, M., Stevaert, A., Naesens, L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015
• Subjects: Acylhydrazones; Animals; Antiviral activity; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Cercopithecus aethiops; Chelating Agents - chemical synthesis; Chelating Agents - chemistry; Chelating Agents - pharmacology; Chelating ligand; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; DNA Viruses - drug effects; Dogs; HeLa Cells; Humans; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Ligands; Magnesium - chemistry; Metal complexes; Metals, Heavy - chemistry; Potentiometry; RNA Viruses - drug effects; Salicylamides - chemical synthesis; Salicylamides - chemistry; Salicylamides - pharmacology; Vero Cells; Acylhydrazones; Chelating ligand; Metal complexes; Antiviral activity
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.05.013

Acylhydrazones are very versatile ligands and their coordination properties can be easily tuned, giving rise to metal complexes with different nuclearities. In the last few years, we have been looking for new pharmacophores able to coordinate simultaneously two metal ions, because many enzymes have two metal ions in the active site and their coordination can be a successful strategy to inhibit the activity of the metalloenzyme. As a part of this ongoing research, we synthesized the acylhydrazone H2L and its complexes with Mg(II), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II). Their characterization, both in solution – also by means of potentiometric studies – and in the solid state, evidenced the ability of the o-vanillin hydrazone scaffold to give rise to different types of metal complexes, depending on the metal and the reaction conditions. Furthermore, we evaluated both the free ligand and its metal complexes in in vitro studies against a panel of diverse DNA- and RNA-viruses. In particular, the Mg(II), Mn(II), Ni(II) and Zn(II) complexes had EC50 values in the low micromolar range, with a pronounced activity against vaccinia virus. An acylhydrazone ligand and its metal complexes show interesting antiviral activity. [Display omitted] •Divalent metal (Mg, Mn, Ni, Zn) complexes with a o-vanillin acylhydrazone ligand are prepared.•The solution chemistry of the new compounds is discussed.•The crystal structures of the copper and cobalt complexes are presented.•The antiviral activity on a panel of DNA- and RNA-viruses is evaluated.