A comparative study of mesoionic compounds in Leishmania sp. and toxicity evaluation

Area of Science:

• Medicinal Chemistry
• Parasitology
• Drug Discovery

Background:

• Leishmaniasis remains a significant global health concern, necessitating the development of novel therapeutic agents.
• Existing treatments for leishmaniasis are associated with toxicity and emerging resistance.
• Mesoionic compounds represent a promising class of molecules with potential therapeutic applications.

Purpose of the Study:

• To synthesize and evaluate a series of 1,3,4-thiadiazolium-2-phenylamine derivatives for antileishmanial activity.
• To assess the in vitro efficacy of these compounds against various Leishmania species, including Leishmania amazonensis, Leishmania chagasi, and Leishmania braziliensis.
• To investigate the cytotoxicity of these novel compounds on host cells, specifically murine macrophages.

Main Methods:

• Synthesis of a series of 1,3,4-thiadiazolium-2-phenylamine derivatives.
• In vitro evaluation of antileishmanial activity against Leishmania amazonensis, Leishmania chagasi, and Leishmania braziliensis.
• Assessment of compound cytotoxicity using murine macrophages.

Main Results:

• The synthesized mesoionic compounds demonstrated in vitro antileishmanial activity against the tested Leishmania species.
• Several halogenated derivatives (compounds 5, 6, 8, and 13) exhibited the highest potency across all Leishmania species.
• The novel compounds displayed lower toxicity in murine macrophages compared to the established antileishmanial drug, pentamidine.

Conclusions:

• 1,3,4-thiadiazolium-2-phenylamine derivatives represent a promising scaffold for the development of new antileishmanial drugs.
• Halogenated derivatives show enhanced efficacy and favorable safety profiles, warranting further investigation.
• These findings contribute to the search for safer and more effective treatments for leishmaniasis.