title: A versatile salicyl hydrazonic ligand and its metal complexes as antiviral agents.
abstract: 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.
authors.affiliation: Dipartimento di Chimica, Parco Area delle Scienze 17/A, 43124 Parma, Italy. Electronic address: dominga.rogolino@unipr.it.
authors.forename: D
authors.initials: D
authors.lastname: Rogolino
authors.affiliation: Dipartimento di Chimica, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Carcelli
authors.affiliation: Dipartimento di Chimica, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bacchi
authors.affiliation: Dipartimento di Farmacia Università di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Compari
authors.affiliation: Dipartimento di Farmacia Università di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Contardi
authors.affiliation: Dipartimento di Farmacia Università di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Fisicaro
authors.affiliation: Dipartimento di Chimica, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gatti
authors.affiliation: Dipartimento di Chimica e Farmacia, Università di Sassari, Via Vienna 2, I-07100 Sassari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sechi
authors.affiliation: Rega Institute for Medical Research, KU Leuven - University of Leuven, B-3000 Leuven, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Stevaert
authors.affiliation: Rega Institute for Medical Research, KU Leuven - University of Leuven, B-3000 Leuven, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Naesens
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004267:DNA Viruses / Q000187:drug effects; D004285:Dogs; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008274:Magnesium / Q000737:chemistry; D019216:Metals, Heavy / Q000737:chemistry; D011199:Potentiometry; D012328:RNA Viruses / Q000187:drug effects; D012457:Salicylamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D006835:Hydrazones; D008024:Ligands; D019216:Metals, Heavy; C000610397:N'-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone; D012457:Salicylamides; D008274:Magnesium
keywords: Acylhydrazones; Antiviral activity; Chelating ligand; Metal complexes