Thymol and eugenol derivatives as potential antileishmanial agents

Area of Science:

• Medicinal Chemistry
• Parasitology
• Drug Discovery

Background:

• Visceral leishmaniasis is a deadly parasitic disease endemic in Northeastern Brazil, with current treatments being toxic and having limited efficacy.
• High mortality rates underscore the urgent need for novel, safer, and more effective therapeutic agents.

Purpose of the Study:

• To synthesize and evaluate novel acetyl and benzoyl derivatives of thymol and eugenol for their antileishmanial activity.
• To identify new molecules with high efficacy and low toxicity against Leishmania infantum chagasi.

Main Methods:

• Synthesized thymol and eugenol derivatives were screened in vitro using luciferase-expressing promastigotes and ELISA in situ for amastigote inhibition.
• In vivo efficacy was assessed in BALB/c mice treated with derivatives, followed by immunohistochemistry to detect parasite presence.

Main Results:

• Thymol derivatives exhibited superior activity compared to eugenol derivatives, with benzoyl-thymol showing the highest inhibitory concentration (8.67 ± 0.28 μg/mL).
• Acetyl-thymol demonstrated enhanced activity against amastigotes compared to thymol and amphotericin B, with no parasites detected in the liver of treated mice.

Conclusions:

• Synthesized thymol and eugenol derivatives possess significant in vitro and in vivo anti-leishmanial activity.
• These compounds represent promising candidates for the development of next-generation treatments for visceral leishmaniasis.