In vitro screening of natural product-based compounds for leishmanicidal activity

Area of Science:

• Medicinal Chemistry
• Parasitology
• Natural Products Chemistry

Background:

• Leishmaniasis is a significant parasitic disease with high mortality and morbidity, lacking a human vaccine.
• Current chemotherapy for leishmaniasis faces challenges including toxicity, long treatment duration, high cost, and drug resistance.
• Natural products, particularly plant-derived compounds like diarylheptanoids, are investigated as alternative sources for anti-leishmanial agents.

Purpose of the Study:

• To synthesize and evaluate novel tetrahydropyran derivatives for their anti-leishmanial activity.
• To assess the toxicity of these derivatives against Leishmania donovani and human macrophages.
• To identify potent and selective anti-leishmanial compounds from the synthesized series.

Main Methods:

• Synthesis of sixteen tetrahydropyran derivatives, including three natural products (Diospongin A, Diospongin B, Centrolobine).
• Evaluation of leishmanicidal activity against Leishmania donovani promastigotes and amastigotes.
• Assessment of cytotoxicity against THP-1-derived human macrophages.
• Calculation of IC50 values and selectivity indices for all tested compounds.

Main Results:

• All sixteen synthesized tetrahydropyran derivatives were tested for their activity and toxicity.
• Five of the synthesized compounds exhibited significant leishmanicidal effects in vitro.
• These five compounds also demonstrated low toxicity to human macrophages, indicating a favorable selectivity index.

Conclusions:

• Tetrahydropyran derivatives represent a promising class of compounds for the development of new anti-leishmanial drugs.
• The synthesized compounds, particularly the five most effective ones, warrant further investigation as potential therapeutic agents against leishmaniasis.
• This study highlights the potential of exploring natural product scaffolds for novel drug discovery in neglected tropical diseases.