Analogues of Marine Guanidine Alkaloids Are in Vitro Effective against Trypanosoma cruzi and Selectively Eliminate Leishmania (L.) infantum Intracellular Amastigotes
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- 2016 Analogues of Marine Guanidine Alkaloids
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DOI
ABSTRACT: Synthetic analogues of marine sponge guanidine
alkaloids showed in vitro antiparasitic activity against
Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines
10 and 11 presented the highest selectivity index when tested
against Leishmania. The antiparasitic activity of 10 and 11 was
investigated in host cells and in parasites. Both compounds
induced depolarization of mitochondrial membrane potential,
upregulation of reactive oxygen species levels, and increased
plasma membrane permeability in Leishmania parasites.
Immunomodulatory assays suggested an NO-independent
effect of guanidines 10 and 11 on macrophages. The same
compounds also promoted anti-inflammatory activity in L. (L.)
infantum-infected macrophages cocultived with splenocytes,
reducing the production of cytokines MCP-1 and IFN-γ.
Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a hostindependent
mechanism.
alkaloids showed in vitro antiparasitic activity against
Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines
10 and 11 presented the highest selectivity index when tested
against Leishmania. The antiparasitic activity of 10 and 11 was
investigated in host cells and in parasites. Both compounds
induced depolarization of mitochondrial membrane potential,
upregulation of reactive oxygen species levels, and increased
plasma membrane permeability in Leishmania parasites.
Immunomodulatory assays suggested an NO-independent
effect of guanidines 10 and 11 on macrophages. The same
compounds also promoted anti-inflammatory activity in L. (L.)
infantum-infected macrophages cocultived with splenocytes,
reducing the production of cytokines MCP-1 and IFN-γ.
Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a hostindependent
mechanism.
| Original language | English |
|---|---|
| Pages (from-to) | 2202-2210 |
| Number of pages | 9 |
| Journal | Journal of natural products |
| Volume | 79 |
| Issue number | 9 |
| Early online date | 2 Sept 2016 |
| DOIs | |
| Publication status | Published - 16 Sept 2016 |
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