Trypanosomatids are protozoan parasites that cause various diseases in human, such as leishmaniasis, Chagas disease and sleeping sickness. The highly syntenic genomes of the trypanosomatid species lead the assumption that they can encode similar proteins, indicating the possibility to design new antitrypanosomatid drugs with dual trypanosomicidal and leishmanicidal activities. In this work a series of compounds (6a-h and 7a-h), containing a semicarbazone scaffold as a peptide mimetic framework, was designed and synthesized. From this series compound 7g (LASSBio-1483) highlighted, showing dual in vitro trypanosomicidal and leishmanicidal activities, with potency similar to the standard drugs nifurtimox and pentamidine. This data, taken together with its good in silico druglikeness profile and its great chemical and plasma stability, make LASSBio-1483 (7g) a new antitrypanosomatid lead-candidate.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2015.05.046 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
New series of 3-pyridyl-1,3-thiazoles: In vitro and in vivo anti-Trypanosomatidae profile, in vitro and in silico mechanism of action approach.
Eur J Med Chem
December 2024
Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil. Electronic address:
Trypanosomatidae diseases, such as Chagas disease and leishmaniasis, are caused by protozoan parasites of the Trypanosomatidae family, namely Trypanosoma cruzi and Leishmania species, respectively. There is an urgent need for new therapies. Both pyridine and thiazole rings are recognized as important scaffolds in medicinal chemistry.
View Article and Find Full Text PDFSynthesis and in vitro leishmanicidal activity of novel N-arylspermidine derivatives.
Bioorg Chem
December 2024
Universidad de Buenos Aires, CONICET, Cátedra de Química Orgánica II, Departamento de Ciencias Químicas, Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina. Electronic address:
This work describes the synthesis and biological evaluation of hitherto unknown N-arylspermidine derivatives 3. Compounds 3 were efficiently prepared from cyclic amidines through a novel synthetic approach comprising alkylation with ω-halonitriles followed by reduction. The cyclic N-arylamidine directs the alkylation to the unsubstituted nitrogen and also provides the N-benzyl group present in the triamine after simultaneous reduction of the resulting quaternary salt 2 and the cyano group.
View Article and Find Full Text PDFMolecular characterization of the E2 conjugating enzyme LinfUbc13 in Leishmania infantum.
Arch Biochem Biophys
December 2024
Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address:
UBC13 is an orthologue of Homo sapiens ubiquitin-conjugation E2 enzymes described in Leishmania mexicana, a null mutant lacking this gene cannot be produced, suggesting essential functions in this parasite. Leishmania infantum is an etiological agent of visceral leishmaniasis, the most severe type of disease that is potentially fatal if untreated. The ubiquitination process has been targeted for leishmanicidal compounds, indicating its essential function in parasite homeostasis.
View Article and Find Full Text PDFLectin from microalgae: Non-toxic to human cells and effective against Leishmania.
Int J Biol Macromol
December 2024
Department of Animal Morphology and Physiology, Federal Rural University of Pernambuco - UFRPE, Dom Manoel de Medeiros Avenue, 52171-900 Recife, PE, Brazil. Electronic address:
New leishmanicidal products are needed for the treatment to be effective, since current drugs are toxic to healthy human/animal cells and have low efficacy against the parasite. Bioactive compounds from microalgae, such as lectins, can be explored as new anti-Leishmania candidates. This study aimed to evaluate the cytotoxic and anti-Leishmania action of the cell extract (CE) and lectin (CVU) from Chlorella vulgaris biomass.
View Article and Find Full Text PDFand Leishmanicidal Activity of Beauvericin.
J Nat Prod
December 2024
Instituto de Biologia, Universidade Estadual de Campinas, Campinas 13083-862, SP, Brazil.
Leishmaniasis is a worldwide disease caused by more than 20 species of parasites. and are among the main causative agents of cutaneous leishmaniasis, presenting a broad spectrum of clinical forms. As these pathologies lead to unsatisfactory treatment outcomes, the discovery of alternative chemotherapeutic options is urgently required.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!