المؤلفون: Daniel Plano, Juan Antonio Palop, Ylenia Baquedano, Carmen Sanmartín, David Moreno, Antonio Jiménez-Ruiz

المصدر: Parasitology Research. 108:233-239

مصطلحات موضوعية: Time Factors, Cell Survival, Antiprotozoal Agents, Pharmacology, Imides, Jurkat cells, Cell Line, Inhibitory Concentration 50, Selenium, chemistry.chemical_compound, Parasitic Sensitivity Tests, medicine, Humans, Leishmania infantum, Amastigote, IC50, Miltefosine, General Veterinary, biology, General Medicine, biology.organism_classification, In vitro, Infectious Diseases, chemistry, Mechanism of action, Insect Science, Parasitology, Carbamates, medicine.symptom, Edelfosine, medicine.drug

الوصف: In the present study, a family of 15 imidothio- and imidoselenocarbamates (1-15) analogs have been synthesized and screened for their in vitro antileishmanial potential against Leishmania infantum promastigotes. The six most active ones (2, 4, 7, 13, 14, and 15) were also tested in an axenic amastigote model. In order to establish their selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1 cell lines. Compounds 2 and 4, both with a pyridine moiety, showed a moderate antileishmanial activity with an IC(50) value of 4.68 ± 0.46 and 3.03 ± 0.24 μM, respectively, in the amastigote model. The activity was compared with that of standard drugs, edelfosine (IC₅₀ = 0.82 ± 0.13 μM) and miltefosine (IC₅₀ = 2.84 ± 0.10 μM). Related to selectivity, the SI of both compounds are similar to those of the standard drugs when compared against the THP-1 cell line. Moreover, compound 4 was able to reduce the number of amastigote-infected THP-1 cells to 40% of that observed in untreated controls after a 96-h period of treatment. These derivatives thus represent two new leads for further studies aimed at establishing their mechanism of action.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3ab80bccb2ae9827190bb3110752874Test
https://doi.org/10.1007/s00436-010-2073-xTest

المؤلفون: Helene Santos Barbosa, R. M. Santa-Rita, S. L. De Castro

المصدر: Parasitology Research. 100:187-190

مصطلحات موضوعية: Chagas disease, Phosphodiesterase Inhibitors, Trypanosoma cruzi, Mitochondrion, chemistry.chemical_compound, parasitic diseases, Organelle, medicine, Animals, Humans, Chagas Disease, Amastigote, Miltefosine, General Veterinary, biology, Phospholipid Ethers, Kinetoplastida, General Medicine, biology.organism_classification, medicine.disease, Microscopy, Electron, Infectious Diseases, Biochemistry, chemistry, Insect Science, Parasitology, Edelfosine, medicine.drug

الوصف: We have previously reported that epimastigote forms of Trypanosoma cruzi treated with the lysophospholipid analogues (LPAs) edelfosine (ET-18), ilmofosine, and miltefosine suffered alterations in plasma membrane, mitochondrion, and lipid synthesis. In this work, ET-18 induced membrane damage in trypomastigotes and amastigotes. Incubation of epimastigotes and trypomastigotes with the three LPAs led to membrane permeabilization, which was abolished by serum addition. Treatment for 24 h in culture medium interfered the with mitochondrial status of epimastigotes, with no effect in trypomastigotes, in agreement with ultrastructural data. LPAs induced alterations in the plasma membrane of the three forms of T. cruzi and in the mitochondria of epimastigotes, suggesting that these organelles are potential targets of these analogues.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e19d7751757bc14614955d661069ce3Test
https://doi.org/10.1007/s00436-006-0250-8Test