Mapping the antileishmanial structure-activity relationship of eugenol
- 1Pharmaceutical Sciences Department, Pacific University School of Pharmacy , , ,
Abstract
Leishmaniasis is a neglected tropical disease with a devastating global impact. The current medications on the market for treating this protozoan parasitic infection are insufficient to fit the global need, with long durations of therapy, growing resistance rates, and severe adverse effects. This investigation aims to characterize an antileishmanial structure-activity relationship for the natural product eugenol. With Leishmania donovani as a model, a series of dose-response curves were performed against eugenol and several of its structural analogs. The same set of compounds was tested against the human monocyte cell THP-1 to characterize their selective toxicity. Subsequently, the pharmacokinetic parameters of the tested compounds were estimated using the in silico modelling software, Percepta®. Eugenol and its analogs demonstrated varying levels of antileishmanial potency, with 4-allylphenol (chavicol) as the most potent compound tested and with the most promising selectivity index. In comparing the potencies and structures of the compounds tested, the data suggests that the para-substituted allyl tail and the phenolic group are important to conferring potency, while the ortho-methoxy substitutions decreased potency. Furthermore, the pharmacokinetic properties of these compounds were predicted to closely resemble eugenol with little risk of cytochrome P450 (CYP) interactions. While more testing is needed to confirm the mechanisms and safety of these compounds, these results suggest eugenol analogs show promise as future antileishmanial therapies.
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BibTeX
@article{daut2026mapping,
title = {{Mapping the antileishmanial structure-activity relationship of eugenol}},
author = {Lucas Daut and Jonathan Taylor and Nicola S. Carter and Brendan D. Stamper},
journal = {Frontiers in pharmacology},
year = {2026},
month = sep,
doi = {10.3389/fphar.2026.1923146},
url = {https://europepmc.org/article/PMC/PMC13661496},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mapping the antileishmanial structure-activity relationship of eugenol
AU - Lucas Daut
AU - Jonathan Taylor
AU - Nicola S. Carter
AU - Brendan D. Stamper
PY - 2026
DA - 2026/09/30
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1923146
UR - https://europepmc.org/article/PMC/PMC13661496
AB - Leishmaniasis is a neglected tropical disease with a devastating global impact. The current medications on the market for treating this protozoan parasitic infection are insufficient to fit the global need, with long durations of therapy, growing resistance rates, and severe adverse effects. This investigation aims to characterize an antileishmanial structure-activity relationship for the natural product eugenol. With Leishmania donovani as a model, a series of dose-response curves were performed against eugenol and several of its structural analogs. The same set of compounds was tested against the human monocyte cell THP-1 to characterize their selective toxicity. Subsequently, the pharmacokinetic parameters of the tested compounds were estimated using the in silico modelling software, Percepta®. Eugenol and its analogs demonstrated varying levels of antileishmanial potency, with 4-allylphenol (chavicol) as the most potent compound tested and with the most promising selectivity index. In comparing the potencies and structures of the compounds tested, the data suggests that the para-substituted allyl tail and the phenolic group are important to conferring potency, while the ortho-methoxy substitutions decreased potency. Furthermore, the pharmacokinetic properties of these compounds were predicted to closely resemble eugenol with little risk of cytochrome P450 (CYP) interactions. While more testing is needed to confirm the mechanisms and safety of these compounds, these results suggest eugenol analogs show promise as future antileishmanial therapies.
SN - 1663-9812
ER -