title: Effects of nitro-heterocyclic derivatives against Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes.
abstract: Leishmaniasis is an overlooked tropical disease affecting approximately 1 million people in several countries. Clinical manifestation depends on the interaction between Leishmania and the host's immune response. Currently available treatment options for leishmaniasis are limited and induce severe side effects. In this research, we tested nitro-heterocyclic compounds (BSF series) as a new alternative against Leishmania. Its activity was measured in Leishmania (Leishmania) infantum promastigotes and intracellular amastigotes using MTT colorimetric assay. Additionally, we assessed the phosphatidylserine exposure by promastigotes, measured by flow cytometry, as well as nitric oxide production, measured by Griess' method. The nitro-heterocyclic compounds (BSF series) showed activity against L. (L.) infantum promastigotes, inducting the phosphatidylserine exposition by promastigotes, decreasing intracellular amastigotes and increasing oxide nitric production. The selectivity index was more prominent to Leishmania than to macrophages. Compared to amphotericin b, our compounds presented higher IC50, however the selectivity index was more specific to parasite than to amphotericin b. In conclusion, these nitro-heterocyclic compounds showed to be promising as an anti-Leishmania drug, in in vitro studies.
authors.affiliation: Laboratório de Soroepidemiologia e Imunobiologia, do Instituto de Medicina Tropical da, Universidade de São Paulo, Brazil.
authors.forename: Simone Carolina Soares
authors.initials: SC
authors.lastname: Petri e Silva
authors.affiliation: Laboratório de Planejamento de Desenvolvimento de Fármacos, Faculdade de Ciências Farmacêuticas da, Universidade de São Paulo, Brazil.
authors.forename: Fanny
authors.initials: F
authors.lastname: Palace-Berl
authors.affiliation: Laboratório de Planejamento de Desenvolvimento de Fármacos, Faculdade de Ciências Farmacêuticas da, Universidade de São Paulo, Brazil.
authors.forename: Leoberto Costa
authors.initials: LC
authors.lastname: Tavares
authors.affiliation: Laboratório de Soroepidemiologia e Imunobiologia, do Instituto de Medicina Tropical da, Universidade de São Paulo, Brazil.
authors.forename: Sandra Regina Castro
authors.initials: SR
authors.lastname: Soares
authors.affiliation: Laboratório de Soroepidemiologia e Imunobiologia, do Instituto de Medicina Tropical da, Universidade de São Paulo, Brazil; Instituto de Infectologia Emilio Ribas-Secretaria de Estado da Saúde de São Paulo, Brazil; Laboratório de Soroepidemiologia (LIM 38 HC-FMUSP), Brazil. Electronic address: jlindoso@usp.br.
authors.forename: José Angelo Lauletta
authors.initials: JA
authors.lastname: Lindoso
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D009000:Monocytes / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009574:Nitro Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010718:Phosphatidylserines / Q000032:analysis
chemical_list: D000981:Antiprotozoal Agents; D006571:Heterocyclic Compounds; D009574:Nitro Compounds; D010718:Phosphatidylserines; D009569:Nitric Oxide
keywords: Apoptosis; Leishmania (L.) infantum; Nitric oxide; Nitroheterocyclic compounds; THP-1 cells