| Full text | |
| Author(s): |
Rosa, Leticia B.
;
Galuppo, Carolina
;
Lima, Rochanna L. A.
;
Fontes, Josielle, V
;
Siqueira, Fabio S.
;
Judice, Wagner A. S.
;
Abbehausen, Camilla
;
Miguel, Danilo C.
Total Authors: 8
|
| Document type: | Journal article |
| Source: | Journal of Inorganic Biochemistry; v. 229, p. 9-pg., 2022-04-01. |
| Abstract | |
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) | |
| FAPESP's process: | 14/02205-1 - Study of kinetic behavior of convertases |
| Grantee: | Wagner Alves de Souza Júdice |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/01678-7 - Cloning, expression and purification of enzyme CRK3 from Leishmania mexicana (LmCRK3) and cycline 6 Leishmania major (LmCYC6) |
| Grantee: | Fábio da Silva Siqueira |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 16/25112-4 - Evaluation of modulators of the activity of proteases involved in pathological processes |
| Grantee: | Wagner Alves de Souza Júdice |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 18/21120-8 - Selective targeting of zinc finger domains with metallodrugs for therapy of parasitic diseases |
| Grantee: | Camilla Abbehausen |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/16904-2 - Targeted metallodrug design for antileishmaniasis |
| Grantee: | Camilla Abbehausen |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/21129-4 - The role of fatty acid-binding proteins in the macrophage infection by Leishmania: a potential target for new drugs against leishmaniasis |
| Grantee: | Danilo Ciccone Miguel |
| Support Opportunities: | Research Grants - Young Investigators Grants |