The in vivo activity of 1,3,4-thiadiazolium-2-aminide compounds in the treatment of cutaneous and visceral leishmaniasis.

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.
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).
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.
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.
AuthorsRaquel F Rodrigues, Karen S Charret, Monica C Campos, Veronica Amaral, Aurea Echevarria, Camila Dos Reis, Marilene M Canto-Cavalheiro, Leonor L Leon
JournalThe Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 67 Issue 1 Pg. 182-90 (Jan 2012) ISSN: 1460-2091 [Electronic] England
PMID21987238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 1,3,4-thiadiazolium-2-aminide
  • Antiprotozoal Agents
  • Organometallic Compounds
  • Thiadiazoles
  • Meglumine
  • meglumine antimoniate
  • Animals
  • Antiprotozoal Agents (administration & dosage, adverse effects)
  • Disease Models, Animal
  • Leishmania infantum (drug effects)
  • Leishmania mexicana (drug effects)
  • Leishmaniasis, Cutaneous (drug therapy)
  • Leishmaniasis, Visceral (drug therapy)
  • Meglumine (administration & dosage)
  • Mice
  • Mice, Inbred BALB C
  • Organometallic Compounds (administration & dosage)
  • Thiadiazoles (administration & dosage, adverse effects)
  • Treatment Outcome

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