Arylthiosemicarbazones as antileishmanial agents

Area of Science:

• Medicinal Chemistry
• Parasitology
• Drug Discovery

Background:

• Leishmaniasis remains a significant global health concern, necessitating the development of new therapeutic agents.
• Existing treatments for leishmaniasis face challenges including toxicity and drug resistance.
• Thiosemicarbazone derivatives have shown potential as antimicrobial and antiparasitic agents.

Purpose of the Study:

• To synthesize and evaluate a series of substituted thiosemicarbazone compounds for antileishmanial activity.
• To identify key structural features responsible for potent anti-parasitic effects.
• To assess the toxicity profile of active compounds against mammalian cell lines.

Main Methods:

• Synthesis of 32 substituted thiosemicarbazone derivatives.
• In vitro evaluation of compound efficacy against intracellular Leishmania donovani amastigotes.
• Determination of half-maximal effective concentration (EC50) and cytotoxicity.

Main Results:

• Twenty-two compounds exhibited EC50 values below 10 μM.
• Compound 14 displayed the highest activity with an EC50 of 0.8 μM.
• The most potent compounds featured fused bicyclic aromatic rings (e.g., naphthalene) with alkyl or alkoxy substituents and showed low mammalian cell toxicity.

Conclusions:

• Substituted thiosemicarbazones, particularly those with naphthalene moieties, are effective antileishmanial agents.
• Compound 14 represents a promising lead candidate for developing novel drugs against leishmaniasis.
• The identified structure-activity relationships can guide future drug design efforts for improved antileishmanial therapies.