Analogues of Marine Guanidine Alkaloids Are <i>in</i> <i>Vitro</i> Effective against <i>Trypanosoma cruzi</i> and Selectively Eliminate <i>Leishmania</i> (<i>L</i>.) <i>infantum</i> Intracellular Amastigotes

Synthetic analogues of marine sponge guanidine alkaloids showed <i>in vitro</i> antiparasitic activity against <i>Leishmania</i> (<i>L.</i>) <i>infantum</i> and <i>Trypanosoma cruzi.</i> Guanidines <b>10</b> and <b>11</b> presented the highest selectivity index when tested against <i>Leishmania</i>. The antiparasitic activity of <b>10</b> and <b>11</b> 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 <i>Leishmania</i> parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines <b>10</b> and <b>11</b> on macrophages. The same compounds also promoted anti-inflammatory activity in <i>L.</i> (<i>L.</i>) <i>infantum</i>-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines <b>10</b> and <b>11</b> affect the bioenergetic metabolism of <i>Leishmania</i>, with selective elimination of parasites via a host-independent mechanism