Rogolino D, Carcelli M, Bacchi A, Compari C, Contardi Laura, Fisicaro E, Gatti A, Sechi M, Stevaert A, Naesens L
Dipartimento di Chimica, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
Dipartimento di Chimica, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
J Inorg Biochem. 2015 Sep;150:9-17. doi: 10.1016/j.jinorgbio.2015.05.013. Epub 2015 May 27.
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.
酰腙是非常通用的配体,其配位性质易于调节,可产生具有不同核数的金属配合物。在过去几年中,我们一直在寻找能够同时配位两个金属离子的新药团,因为许多酶的活性位点中有两个金属离子,它们的配位可能是抑制金属酶活性的成功策略。作为这项正在进行的研究的一部分,我们合成了酰腙H2L及其与Mg(II)、Mn(II)、Co(II)、Ni(II)、Cu(II)和Zn(II)的配合物。它们在溶液中的表征——也通过电位滴定研究——以及在固态中的表征,证明了邻香草醛腙支架根据金属和反应条件产生不同类型金属配合物的能力。此外,我们在体外研究中评估了游离配体及其金属配合物对多种DNA和RNA病毒的活性。特别是,Mg(II)、Mn(II)、Ni(II)和Zn(II)配合物的EC50值在低微摩尔范围内,对痘苗病毒具有显著活性。