Activity of the Di-Substituted Urea-Derived Compound I-17 in <i>Leishmania</i> In Vitro Infections
José Vitorino dos Santos,
Jorge Mansur Medina,
Karina Luiza Dias Teixeira,
Daniel Marcos Julio Agostinho,
Michael Chorev,
Aurora Diotallevi,
Luca Galluzzi,
Bertal Huseyin Aktas,
Ulisses Gazos Lopes
Affiliations
José Vitorino dos Santos
Laboratory of Molecular Parasitology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Jorge Mansur Medina
Laboratory of Molecular Parasitology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Karina Luiza Dias Teixeira
Department of Cell Biology, University of Virginia, Pinn Hall, Charlottesville, VA 22908, USA
Daniel Marcos Julio Agostinho
Laboratory of Molecular Parasitology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Michael Chorev
Division of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Aurora Diotallevi
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
Luca Galluzzi
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
Bertal Huseyin Aktas
Division of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Ulisses Gazos Lopes
Laboratory of Molecular Parasitology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil
Protein synthesis has been a very rich target for developing drugs to control prokaryotic and eukaryotic pathogens. Despite the development of new drug formulations, treating human cutaneous and visceral Leishmaniasis still needs significant improvements due to the considerable side effects and low adherence associated with the current treatment regimen. In this work, we show that the di-substituted urea-derived compounds I-17 and 3m are effective in inhibiting the promastigote growth of different Leishmania species and reducing the macrophage intracellular load of amastigotes of the Leishmania (L.) amazonensis and L. major species, in addition to exhibiting low macrophage cytotoxicity. We also show a potential immunomodulatory effect of I-17 and 3m in infected macrophages, which exhibited increased expression of inducible Nitric Oxide Synthase (NOS2) and production of Nitric Oxide (NO). Our data indicate that I-17, 3m, and their analogs may be helpful in developing new drugs for treating leishmaniasis.
