ArticleAntimicrobial agents and chemotherapy2006
Aziridine-2,3-dicarboxylates, peptidomimetic cysteine protease inhibitors with antileishmanial activity.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 60 citations in OpenAlex.
- Antileishmanial Activity ofPlants (Basel, Switzerland) · 2023Article
- Amino Acid Based Antimicrobial Agents - Synthesis and Properties.ChemMedChem · 2021Review
- Leishmanicidal Activity of Betulin Derivatives inMicroorganisms · 2021Article
- Coccinia grandis (L.) Voigt Leaf Extract Exhibits Antileishmanial Effect Through Pro-inflammatory Response: An In Vitro Study.Current microbiology · 2017Article
- Development of a New Antileishmanial Aziridine-2,3-Dicarboxylate-Based Inhibitor with High Selectivity for Parasite Cysteine Proteases.Antimicrobial agents and chemotherapy · 2016Article
- Article
- Why strategies to control Leishmania spp. multiplication based on the use of proteinase inhibitors should consider multiple targets and not only a single enzyme.Journal of molecular modeling · 2014Article
- Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection.PLoS neglected tropical diseases · 2014Article
- Production of induced secondary metabolites by a co-culture of sponge-associated actinomycetes, Actinokineospora sp. EG49 and Nocardiopsis sp. RV163.Marine drugs · 2014Article
- Actinomycetes from Red Sea sponges: sources for chemical and phylogenetic diversity.Marine drugs · 2014Article
- Identification of plakortide E from the Caribbean sponge Plakortis halichondroides as a trypanocidal protease inhibitor using bioactivity-guided fractionation.Marine drugs · 2014Article
- Evaluation of the Leishmanicidal Activity of Rutaceae and Lauraceae Ethanol Extracts on Golden Syrian Hamster (Mesocricetus auratus) Peritoneal Macrophages.Indian journal of pharmaceutical sciences · 2014Article
- Nonproteinogenic amino acid building blocks for nonribosomal peptide and hybrid polyketide scaffolds.Angewandte Chemie (International ed. in English) · 2013Review
- A novel Leishmania major amastigote assay in 96-well format for rapid drug screening and its use for discovery and evaluation of a new class of leishmanicidal quinolinium salts.Antimicrobial agents and chemotherapy · 2013Article
- In vitro and in vivo activity of a palladacycle complex on Leishmania (Leishmania) amazonensis.PLoS neglected tropical diseases · 2012Article
- Valeriana wallichii root extracts and fractions with activity against Leishmania spp.Parasitology research · 2011Article
- Current developments in the therapy of protozoan infections.The open medicinal chemistry journal · 2011Article
- New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities.Marine drugs · 2011Article
- Mode-of-action studies of the novel bisquaternary bisnaphthalimide MT02 against Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2011Article
- Aziridine-2,3-dicarboxylate-based cysteine cathepsin inhibitors induce cell death in Leishmania major associated with accumulation of debris in autophagy-related lysosome-like vacuoles.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy of leishmaniasis is mainly based on antimonials. However, they are extremely toxic and cause serious side effects, and there is a worldwide increasing frequency of chemoresistance to antimonials. These issues emphasize the urgent need for affordable alternative drugs against leishmaniasis. Leishmania cysteine proteases are essential for parasite growth, differentiation, pathogenicity, and virulence and are thus attractive targets for combating leishmaniasis. Herein we demonstrate that the cysteine protease inhibitors aziridine-2,3-dicarboxylates 13b and 13e impaired promastigote growth at mid-micromolar concentrations and decreased the infection rate of peritoneal macrophages at concentrations 8- to 13-fold lower than those needed to inhibit parasite replication. Simultaneous treatment of infected cells with compound 13b and gamma interferon resulted in an even further reduction of the concentration needed for a significant decrease in macrophage infection rate. Notably, treatment with the compounds alone modulated the cytokine secretion of infected macrophages, with increased levels of interleukin-12 and tumor necrosis factor alpha. Furthermore, the decreased infection rate in the presence of compound 13b correlated with increased nitric oxide production by macrophages. Importantly, at the concentrations used herein, compounds 13b and 13e were not toxic against fibroblasts, macrophages, or dendritic cells. Together, these results suggest that the aziridine-2,3-dicarboxylates 13b and 13e are potential antileishmanial lead compounds with low toxicity against host cells and selective antiparasitic effects.
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