ArticlePLoS neglected tropical diseases2015
Targeting Ergosterol biosynthesis in Leishmania donovani: essentiality of sterol 14 alpha-demethylase.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 121 citations in OpenAlex.
- Sterol Endoperoxides and Their Antileishmanial Effects: Influence on Viability, Oxygen Metabolism and Sterol Synthesis.Molecules (Basel, Switzerland) · 2026Article
- Heme limitation induces LHR2, an essential gene for Leishmania pathogenesis.PLoS pathogens · 2026Article
- Resistance of ERG24 sterol C-14 reductase to heterocyclic amine antifungals.npj antimicrobials and resistance · 2025Article
- C14DM Ablation Leads to Reduced Tolerance to Plasma Membrane Stress and Increased Drug Sensitivity inInternational journal of molecular sciences · 2025Article
- Identification of Substituted 4-Aminocinnolines as Broad-Spectrum Antiparasitic Agents.ACS infectious diseases · 2025Article
- Progress in antileishmanial drugs: Mechanisms, challenges, and prospects.PLoS neglected tropical diseases · 2025Review
- Leishmania protein KMP-11 modulates cholesterol transport and membrane fluidity to facilitate host cell invasion.EMBO reports · 2024Article
- N-substituted-4-(pyridin-4-ylalkyl)piperazine-1-carboxamides and related compounds as Leishmania CYP51 and CYP5122A1 inhibitors.Bioorganic & medicinal chemistry · 2024Article
- Possibility of re-purposing antifungal drugs posaconazole & isavuconazole against promastigote form of Leishmania major.The Indian journal of medical research · 2024Article
- CYP5122A1 encodes an essential sterol C4-methyl oxidase in Leishmania donovani and determines the antileishmanial activity of antifungal azoles.Nature communications · 2024Article
- Novel Diacyl-hydrazide Compounds as Potential Therapeutics for Visceral Leishmaniasis.ACS omega · 2024Article
- Sterol 14-alpha demethylase (CYP51) activity in Leishmania donovani is likely dependent upon cytochrome P450 reductase 1.PLoS pathogens · 2024Article
- Leishmanicidal and immunomodulatory activity ofHeliyon · 2024Article
- An updated review of the pharmacological effects and potential mechanisms of hederagenin and its derivatives.Frontiers in pharmacology · 2024Review
- Live attenuated-nonpathogenicFrontiers in microbiology · 2024Review
- Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major.PLoS pathogens · 2023Article
- Fatty Acid Composition and Metabolism inInternational journal of molecular sciences · 2023Review
- Ethanolaminephosphate cytidyltransferase is essential for survival, lipid homeostasis and stress tolerance inbioRxiv : the preprint server for biology · 2023Article
- Systems biology of autophagy in leishmanial infection and its diverse role in precision medicine.Frontiers in molecular biosciences · 2023Review
- Discovery of pyrazolopyrrolidinones as potent, broad-spectrum inhibitors ofFrontiers in tropical diseases · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Leishmania protozoan parasites (Trypanosomatidae family) are the causative agents of cutaneous, mucocutaneous and visceral leishmaniasis worldwide. While these diseases are associated with significant morbidity and mortality, there are few adequate treatments available. Sterol 14alpha-demethylase (CYP51) in the parasite sterol biosynthesis pathway has been the focus of considerable interest as a novel drug target in Leishmania. However, its essentiality in Leishmania donovani has yet to be determined. Here, we use a dual biological and pharmacological approach to demonstrate that CYP51 is indispensable in L. donovani. We show via a facilitated knockout approach that chromosomal CYP51 genes can only be knocked out in the presence of episomal complementation and that this episome cannot be lost from the parasite even under negative selection. In addition, we treated wild-type L. donovani and CYP51-deficient strains with 4-aminopyridyl-based inhibitors designed specifically for Trypanosoma cruzi CYP51. While potency was lower than in T. cruzi, these inhibitors had increased efficacy in parasites lacking a CYP51 allele compared to complemented parasites, indicating inhibition of parasite growth via a CYP51-specific mechanism and confirming essentiality of CYP51 in L. donovani. Overall, these results provide support for further development of CYP51 inhibitors for the treatment of visceral leishmaniasis.
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