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Background: Leishmaniasis reaches millions of people around the world. The control of the disease is difficult due to the restricted access to the diagnosis and medication, and low adherence to the treatment. Thus, more efficient drugs are needed and natural products are good alternatives. Iridoids, natural products with reported leishmanicidal activity, can be exploited for the development of anti- Leishmania drugs. The aim of this study was to isolate and to investigate the in vitro activity of iridoids against Leishmania amazonensis and to compare the activity in silico of these compounds with those reported as active against this parasite.
Methods: Iridoids were isolated by chromatographic methods. The in vitro activity of asperuloside (1) and geniposide (2) from Escalonia bifida, galiridoside (3) from Angelonia integerrima and theveridoside (4) and ipolamiide (5) from Amphilophium crucigerum was investigated against promastigote forms of Leishmania amazonensis. Molecular modeling studies of 1-5 and iridoids cited as active against Leishmania spp. were performed.
Results: Compounds 1-5 (5-100 µM) did not inhibit the parasite survival. Physicochemical parameters predicted for 1-5 did not show differences compared to those described in literature. The SAR and the pharmacophoric model confirmed the importance of maintaining the cyclopentane[C]pyran ring of the iridoid, of oxygen-linked substituents at the C1 and C6 positions and of bulky substituents attached to the iridoid ring to present leishmanicidal activity.
Conclusion: The results obtained in this study indicate that iridoids are a promising group of secondary metabolites and should be further investigated in the search for new anti-Leishmania drugs.
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http://dx.doi.org/10.2174/1570163814666171002102058 | DOI Listing |
Front Cell Infect Microbiol
December 2024
Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montréal, QC, Canada.
The study of extracellular vesicles has become an incredibly important field of study, but the inherent heterogeneity of these vesicles continues to make their study challenging. The genetic variability and well-documented protocols for the growth and vesicle isolation from parasites provide a unique opportunity to compare the heterogeneity of different populations secreted by clones. was cultured on solid SDM agar plates and 8 clonal colonies were selected.
View Article and Find Full Text PDFArch 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 PDFBiochem Pharmacol
December 2024
Instituto de Biologia, Universidade Estadual de Campinas - UNICAMP, Campinas, São Paulo, Brazil. Electronic address:
Leishmaniasis is one of the most important neglected diseases, classically characterized by three clinical forms that if left untreated can lead to skin lesions, lifelong scarring, or death depending on the parasite species. Unfortunately, treatment is unsatisfactory and the search for an improved therapy has been a priority. Gold compounds have emerged as promising candidates and among them, Au(I)bis-N-heterocyclic carbene (Au(BzTMX)) has stood out.
View Article and Find Full Text PDFJ Leukoc Biol
December 2024
Immunobiotechnology Laboratory, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
γδ T cells play diverse roles in immune responses, producing either IL-17A or IFN-γ. Here we investigated the impact of this functional dichotomy on cutaneous leishmaniasis. We demonstrate that in Sv129 mice susceptible to Leishmania amazonensis, Vγ4+ γδ T cells are the main source of IL-17A.
View Article and Find Full Text PDFJ Photochem Photobiol B
December 2024
Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco (UFPE), Recife, Pernambuco 50670-901, Brazil. Electronic address:
The current chemotherapy for cutaneous leishmaniasis (CL) is accompanied by side effects and drug resistance emergence, encouraging the proposal of new treatment approaches for this disease. ZnTnHex-2-PyP (ZnP hexyl) is a water-soluble Zn(II) porphyrin that exhibits remarkable potential for photodynamic therapy (PDT). This study aimed to investigate the ZnP hexyl-PDT against CL in vivo.
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