Antiviral Activity of Pd(II) Complexes with Aminoadamantanes Against Arboviruses

In this paper, we report the synthesis, structural characterization, and antiviral properties of palladium(II) complexes with amantadine (atd) and memantine (mtn). Elemental and mass spectrometric analyses indicated a 1:2 metal/ligand ratio. The single crystal data for Pd-mtn revealed that the complex adopts a square geometry with the two memantine ligands bonded to Pd(II) by the nitrogen atoms of the NH2 group, in a trans configuration. Computational studies supported a similar structure for Pd-atd. The complexes were stable in DMSO solution for 24 h. The antiviral properties of Pd-atd and Pd-mtn were evaluated against Zika (ZIKV) and Chikungunya (CHIKV) viruses in vitro at their highest noncytotoxic concentrations. The Pd-atd (at 2 µM) and Pd-mtn (at 10 µM) complexes were able to impair 76% and 96% of CHIKV replication, respectively, which points the coordination of amantadine and memantine to Pd(II) as a successful strategy to increase their anti-CHIKV properties. Conversely, the Pd(II) complexes did not significantly inhibit the replication of ZIKV, which confirms the selectivity towards CHIKV. Interaction of the compounds with N-acetyl-l-cysteine, a model disulfide-containing peptide, and plasmid DNA pointed to Cys-containing peptides as more likely targets than nucleotides for the complexes.