Exploring antiviral and antiparasitic activity of gold N-heterocyclic carbenes with thiolate ligands

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Oliveira, Igor S. ; Garcia, Marcus S. A. ; Cassani, Natasha M. ; Oliveira, Ana L. C. ; Freitas, Lara C. F. ; Bertolini, Vitor K. S. ; Castro, Jennyfer ; Clauss, Gustavo ; Honorato, Joao ; Gadelha, Fernanda R. ; Miguel, Danilo C. ; Jardim, Ana C. G. ; Abbehausen, Camilla

• Tipo de documento: Artigo Científico
• Fonte: DALTON TRANSACTIONS; v. 53, n. 47, p. 11-pg., 2024-08-15.

Resumo

Gold(i) N-heterocyclic carbenes have been explored for their therapeutic potential against several diseases. Neglected tropical diseases, including leishmaniasis, Chagas disease, and viral infections, such as zika, mayaro, and chikungunya, urgently require new treatment options. The emergent SARS-CoV-2 also demands significant attention. Gold complexes have shown promise as alternative treatments for these conditions. Previously, gold(i)(1,3-bis(mesityl)imidazole-2-ylidene)Cl (AuIMesCl) demonstrated significant leishmanicidal and anti-Chikungunya virus activities. In this study, we synthesized and fully characterized a series of gold(i)(1,3-bis(mesityl)imidazole-2-ylidene)(SR) complexes, where SR includes thiolate donor species such as 1,3-thiazolidine-2-thione, 1,3-benzothiazole-2-thione, 2-mercaptopyrimidine, and 2-thiouracil. These compounds were stable in solution, and ligand exchange reactions with N-acetyl-l-cysteine indicated that complexes with SR ligands are more labile than those with chloride. Although the reactions are rapid, they reach equilibrium at varying molar ratios depending on the SR ligand. The increased lability of these compounds results in higher cytotoxicity to host cells, such as Vero E6 and bone marrow-differentiated macrophages, compared to AuIMesCl. Despite this, the compounds effectively inhibited viral replication, achieving 95.5% inhibition of Zika virus replication at 2 mu M with 96% host cell viability. Although active at low concentrations (similar to 2 mu M) against Leishmania (L.) amazonensis and Trypanosoma cruzi, their high cytotoxicity for macrophages confirmed AuIMesCl as a better candidate with a higher selectivity index. This work correlates the coordination chemistry of pyrimidines and thiazolidines with their in vitro biological activities against significant diseases. Novel gold(i)(NHC) containing thiopyrimidines and thiazolidines with promising antiviral and antiparasitic activity. (AU)

• Processo FAPESP: 22/02618-0 - Desenvolvimento de novos metalofármacos e formas de administração inovadoras para tratamento de Leishmaniose
• Beneficiário: Camilla Abbehausen
• Modalidade de apoio: Auxílio à Pesquisa - Projeto Inicial
• Processo FAPESP: 23/06493-0 - Implementação de rotina de cultura celular de mamíferos
• Beneficiário: Karen Caroline Minori Vieira
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 23/12657-6 - Análise computacional de complexos de ouro (I) como metalofármacos em terapias alvo à Leishmaniose
• Beneficiário: Gustavo Clauss Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto