| Texto completo | |
| Autor(es): |
Fontes, J. V.
;
Agnoli, M. E. F.
;
Clauss, G.
;
Garcia, M. S. A.
;
Ferreira, A. V. P.
;
Antoniucci, G. A.
;
Costa-Oliveira, A. L.
;
Jardim, A. C. G.
;
Miguel, D. C.
;
Abbehausen, C.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CHEMISTRYSELECT; v. 10, n. 31, p. 9-pg., 2025-08-11. |
| Resumo | |
In this study, we investigated the activity and properties of three neutral Cu(I) N-heterocyclic carbene (NHC) complexes-[1,3-bis(2,6-diisopropylphenyl) imidazol-2-ylidene]copper(I) with Cl, Br, and I, specifically [Cu(IPr)Cl], [Cu(IPr)Br], and [Cu(IPr)I]-to evaluate the impact of halogen substitution on anti-Leishmania and antiviral activity. The compounds were synthesized using reported methods. 13C NMR spectroscopy provided insights into the electronic nature of the Cu & horbar;X bond by analyzing the NHC C2 chemical shift. Notably, the iodine derivative exhibited distinct chemical properties compared to its counterparts, displaying a more covalent Cu & horbar;I bond. As a result, [Cu(IPr)I] was more susceptible to nucleophilic attack, as confirmed by HOMO-LUMO gap calculations using DFT. Furthermore, this derivative demonstrated the highest lipophilicity and the strongest antioxidant activity in the series, as evidenced by the DPPH assay, surpassing butylated hydroxytoluene (BHT) used as a positive control. Bovine serum albumin (BSA) binding assays indicated weak interaction (103 M-1) across all compounds, with no significant differences observed. In anti-Leishmania assays, [Cu(IPr)I] exhibited the best selectivity index (SI = 4.0), showing greater toxicity to the parasite (EC50 = 1.5 mu M) while being less toxic to the host cell (CC50 = 6.0 mu M). However, this trend did not extend to antiviral studies against the chikungunya virus, where [Cu(IPr)Br] displayed the highest replication inhibition (EC50 = 0.807 mu M) and the best selectivity index (SI = 4.8). Our findings highlight that halogen substitution plays a crucial role in modulating the biological activity of neutral linear metal-NHC complexes. (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: | 22/06410-5 - Complexos metálicos como inibidores enzimáticos específicos para o tratamento da Leishmaniose: cisteína protease e tripanotiona redutase |
| Beneficiário: | Josielle Vieira Fontes |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| 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 |