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Article

Sterol Endoperoxides and Their Antileishmanial Effects: Influence on Viability, Oxygen Metabolism and Sterol Synthesis

by
Deblina Sarkar
1,2,
Azra Aleta
1,
Moris Ahmetašević
1,
Mira Tosin
1,
Laura Machin
1,3,
Elisabeth Schrödl
1,
Markus Bacher
4,
Thomas Rosenau
4,
Lianet Monzote
5,
Katrin Staniek
1,
Mitali Chatterjee
2 and
Lars Gille
1,*
1
Pharmacology and Toxicology, Department of Biological Sciences and Pathobiology, University of Veterinary Medicine, 1210 Vienna, Austria
2
Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata 700 020, India
3
Pharmacy Department, Institute of Pharmacy and Food Sciences, University of Havana, Havana 13600, Cuba
4
Institute of Chemistry of Renewable Resources, Department of Natural Sciences and Sustainable Resources, UFT Research Center, BOKU University, 3430 Tulln, Austria
5
Parasitology Department, Institute of Tropical Medicine “Pedro Kouri”, Havana 17100, Cuba
*
Author to whom correspondence should be addressed.
Molecules 2026, 31(6), 979; https://doi.org/10.3390/molecules31060979
Submission received: 21 January 2026 / Revised: 2 March 2026 / Accepted: 9 March 2026 / Published: 14 March 2026
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Leishmaniasis is a global health issue, especially in tropical and subtropical areas, with treatment challenges due to the development of resistance to current drugs. This has prompted the search for new antileishmanial compounds. Endoperoxides, due to parasites’ reliance on external iron and susceptibility to oxidative stress, are promising antileishmanial compounds. This study evaluated two sterol endoperoxides—ergosterol endoperoxide (ErgoEP) and dehydrocholesterol endoperoxide (DHCholEP)—for their antileishmanial activity and mechanism in vitro. Cell viability assays with Leishmania donovani and Leishmania tarentolae promastigotes showed IC50 values in the low micromolar range (from 2.0 to 4.5 µM, respectively) with low toxicity to murine and J774A.1 macrophages. Electron paramagnetic resonance spectroscopy confirmed radical generation in the presence of low-molecular-weight iron compounds. However, this did not trigger the antileishmanial effect, as neither N-acetylcysteine nor pyridoxal isonicotinoyl hydrazone altered activity. Mitochondrial function(s) and superoxide production in Leishmania remained unaffected. Both endoperoxides significantly inhibited synthesis of 5-dehydroepisterol, the major sterol in Leishmania tarentolae, suggesting targeting of the sterol biosynthesis pathway. Their limited toxicity to mammalian macrophages makes ergosterol and dehydrocholesterol endoperoxides promising candidates for future antileishmanial drug development.
Keywords: Leishmania; macrophages; sterol endoperoxides; mitochondria; viability; 5-dehydroepisterol Leishmania; macrophages; sterol endoperoxides; mitochondria; viability; 5-dehydroepisterol

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MDPI and ACS Style

Sarkar, D.; Aleta, A.; Ahmetašević, M.; Tosin, M.; Machin, L.; Schrödl, E.; Bacher, M.; Rosenau, T.; Monzote, L.; Staniek, K.; et al. Sterol Endoperoxides and Their Antileishmanial Effects: Influence on Viability, Oxygen Metabolism and Sterol Synthesis. Molecules 2026, 31, 979. https://doi.org/10.3390/molecules31060979

AMA Style

Sarkar D, Aleta A, Ahmetašević M, Tosin M, Machin L, Schrödl E, Bacher M, Rosenau T, Monzote L, Staniek K, et al. Sterol Endoperoxides and Their Antileishmanial Effects: Influence on Viability, Oxygen Metabolism and Sterol Synthesis. Molecules. 2026; 31(6):979. https://doi.org/10.3390/molecules31060979

Chicago/Turabian Style

Sarkar, Deblina, Azra Aleta, Moris Ahmetašević, Mira Tosin, Laura Machin, Elisabeth Schrödl, Markus Bacher, Thomas Rosenau, Lianet Monzote, Katrin Staniek, and et al. 2026. "Sterol Endoperoxides and Their Antileishmanial Effects: Influence on Viability, Oxygen Metabolism and Sterol Synthesis" Molecules 31, no. 6: 979. https://doi.org/10.3390/molecules31060979

APA Style

Sarkar, D., Aleta, A., Ahmetašević, M., Tosin, M., Machin, L., Schrödl, E., Bacher, M., Rosenau, T., Monzote, L., Staniek, K., Chatterjee, M., & Gille, L. (2026). Sterol Endoperoxides and Their Antileishmanial Effects: Influence on Viability, Oxygen Metabolism and Sterol Synthesis. Molecules, 31(6), 979. https://doi.org/10.3390/molecules31060979

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