title: The in vivo activity of 1,3,4-thiadiazolium-2-aminide compounds in the treatment of cutaneous and visceral leishmaniasis.
abstract: OBJECTIVE
  Researchers have recently investigated the biological activities of mesoionic (MI) compounds, which have shown in vitro activity against many species of Leishmania, as well as Trypanosoma cruzi. The main goal of this study was to evaluate and compare the activity of three MI compounds against Leishmania amazonensis and Leishmania infantum infection in vivo.
  
  
  METHODS
  The experiments were carried out using BALB/c mice infected with L. amazonensis or L. infantum as a highly sensitive murine model. The infected mice were treated with MI-HH, MI-4-OCH(3), MI-4-NO(2) or meglumine antimoniate by different routes (intralesional, topical or intraperitoneal).
  
  
  RESULTS
  Treatment with MI-4-OCH(3) and MI-4-NO(2) efficiently contained the progression of cutaneous and visceral leishmaniasis in comparison with the control group or mice treated with meglumine antimoniate. Interestingly, these MI compounds did not produce toxicological effects after treatment. Furthermore, treatment with these compounds led to a modulation of the immune response that was correlated with disease control. In this study, MI compounds, and MI-4-NO(2) in particular, exhibited high activity in the L. infantum murine model. In the L. amazonensis model, intralesional treatment with MI-4-OCH(3) or MI-4-NO(2) showed greater therapeutic efficacy than treatment with meglumine antimoniate, and the new topical formulations of these compounds also displayed great activity in the cutaneous leishmaniasis model.
  
  
  CONCLUSIONS
  Upon comparison of each MI compound, MI-4-NO(2) was clearly the compound with the greatest activity in these two in vivo infection models by each administration route tested.
authors: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Tripanosomatídeos, Rio de Janeiro, Brasil. rakelbio@gmail.com
authors: Raquel F
authors: RF
authors: Rodrigues
authors: Karen S
authors: KS
authors: Charret
authors: Monica C
authors: MC
authors: Campos
authors: Veronica
authors: V
authors: Amaral
authors: Aurea
authors: A
authors: Echevarria
authors: Camila
authors: C
authors: Dos Reis
authors: Marilene M
authors: MM
authors: Canto-Cavalheiro
authors: Leonor L
authors: LL
authors: Leon
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004195:Disease Models, Animal; D018314:Leishmania infantum / Q000187:drug effects; D007894:Leishmania mexicana / Q000187:drug effects; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008536:Meglumine / Q000008:administration & dosage; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage; D013830:Thiadiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: C539945:1,3,4-thiadiazolium-2-aminide; D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D013830:Thiadiazoles; D008536:Meglumine; D000077485:Meglumine Antimoniate