| Texto completo | |
| Autor(es): |
Rosa, Leticia B.
;
Galuppo, Carolina
;
Lima, Rochanna L. A.
;
Fontes, Josielle, V
;
Siqueira, Fabio S.
;
Judice, Wagner A. S.
;
Abbehausen, Camilla
;
Miguel, Danilo C.
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Inorganic Biochemistry; v. 229, p. 9-pg., 2022-04-01. |
| Resumo | |
Leishmania amazonensis and L. braziliensis are the main etiological agents of the American Tegumentary Leish-maniasis (ATL). Taking into account the limited effectiveness and high toxicity of the current drug arsenal to treat ATL, novel options are urgently needed. Inspired by the fact that gold-based compounds are promising candidates for antileishmanial drugs, we studied the biological action of a systematic series of six (1)-(6) sym-metric Au(I) benzyl and aryl-N-heterocyclic carbenes. All compounds were active at low micromolar concen-trations with 50% effective concentrations ranging from 1.57 to 8.30 mu M against Leishmania promastigotes. The mesityl derivative (3) proved to be the best candidate from this series, with a selectivity index ~13 against both species. The results suggest an effect of the steric and electronic parameters of the N-substituent in the activity. Intracellular infections were drastically reduced after 24h of (2)-(5) incubation in terms of infection rate and amastigote burden. Further investigations showed that our compounds induced significant parasites' morpho-logical alterations and membrane permeability. Also, (3) and (6) were able to reduce the residual activity of three Leishmania recombinant cysteine proteases, known as possible targets for Au(I) complexes. Our promising results open the possibility of exploring gold complexes as leishmanicidal molecules to be further screened in in vivo models of infection. (AU) | |
| Processo FAPESP: | 14/02205-1 - Estudo do comportamento cinético das convertases |
| Beneficiário: | Wagner Alves de Souza Júdice |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/01678-7 - Clonagem, expressão e purificação da enzima CRK3 de Leishmania mexicana (LmCRK3) e ciclina 6 de Leishmania major (LmCYC6) |
| Beneficiário: | Fábio da Silva Siqueira |
| Modalidade de apoio: | Bolsas no Brasil - Iniciação Científica |
| Processo FAPESP: | 16/25112-4 - Avaliação de moduladores da atividade de proteases envolvidas em processos patológicos |
| Beneficiário: | Wagner Alves de Souza Júdice |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 18/21120-8 - Metalofármacos inibidores seletivos de zinc fingers para o tratamento de doenças parasitárias |
| Beneficiário: | Camilla Abbehausen |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 19/16904-2 - Metalofármacos direcionados a alvos específicos para o tratamento de leishmaniose |
| Beneficiário: | Camilla Abbehausen |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 14/21129-4 - O papel das proteínas ligantes de ácidos graxos na infecção de macrófagos por Leishmania: um alvo potencial para novas drogas contra leishmaniose |
| Beneficiário: | Danilo Ciccone Miguel |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |