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

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Silva, Laura Barros ; Cruz, allefe Barbosa ; Pereira, Douglas Henrique ; Cassani, Natasha Marques ; Ruiz, Uriel Enrique Aquino ; Santos, Igor Andrade ; Martins, Daniel Oliveira Silva ; Nakahata, Douglas Hideki ; Simoni, Deborah de Alencar ; Kanavos, Ioannis ; Ronga, Luisa ; Lobinski, Ryszard ; dos Santos Pereira, Anna Karla ; Gomes Jardim, Ana Carolina ; de Paiva, Raphael Enoque Ferraz ; Corbi, Pedro Paulo

• Document type: Journal article
• Source: CHEMISTRYSELECT; v. 9, n. 37, p. 11-pg., 2024-10-01.

Abstract

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 mu M) and Pd-mtn (at 10 mu M) 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. (AU)

• FAPESP's process: 21/10265-8 - Cancer Theranostics Innovation Center (CancerThera)
• Grantee: Carmino Antonio de Souza
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 22/08320-3 - Synthesis, characterization and antiviral activity studies of Pd(II) with aminoadamantanes complexes
• Grantee: Laura Barros Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 21/08717-8 - Synthesis of copper, silver and gold complexes involving nucleotide analogues in the search of new alternatives for the treatment of ovarian cancer
• Grantee: Pedro Paulo Corbi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/11485-6 - Computational and theoretical developments based on ab initio methods and the Density Functional Theory
• Grantee: Rogério Custodio
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/08293-7 - CCES - Center for Computational Engineering and Sciences
• Grantee: Munir Salomao Skaf
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 23/14245-7 - SYNTHESIS, CHARACTERIZATION AND ANTIVIRAL STUDIES OF NOVEL Pd(II) COMPLEXES WITH AMINOADAMANTANES
• Grantee: Laura Barros Silva
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation