Antileishmanial activity of 3,4,5-trisubstituted isoxazoles by interaction with Leishmania amazonensis plasma membrane

2022 ◽  
Vol 1249 ◽  
pp. 131604
Author(s):  
Lais Alonso ◽  
Karlos Eduardo Pianoski ◽  
Antonio Alonso ◽  
Fernanda Andreia Rosa
2018 ◽  
Vol 4 ◽  
Author(s):  
Juliana Q. Reimão ◽  
Silvia R. B. Uliana

Abstract The treatment of leishmaniasis relies primarily on highly toxic, parenterally administered drugs. Therefore, the search for more effective and safer drugs is considered a priority for leishmaniasis’ control. The antileishmanial activity of the oestrogen receptor modulator tamoxifen was previously described in experimental models of leishmaniasis. However, the mechanisms responsible for the antileishmanial activity of tamoxifen remain unknown. Since tamoxifen has been shown to affect plasma and intracellular membranes in tumour cells, the aim of this study was to investigate the activity of the drug on Leishmania amazonensis membranes. Through morphological analysis and labelling with propidium iodide and DiSBAC2(3), we demonstrated that tamoxifen led to plasma membrane depolarization without general membrane disruption or permeabilization. Tamoxifen also caused mitochondrial damage, with loss of membrane potential, as shown by Rhodamine 123 accumulation. Mitochondrial swelling followed, signalling the mitochondrial dysfunction. Therefore, the effect of tamoxifen on Leishmania is mediated, at least in part, by disorder in parasite's membranes. These alterations are sufficient to trigger a series of lethal events.


2021 ◽  
Vol 140 ◽  
pp. 68-75
Author(s):  
Lucas Moreira Brito ◽  
Michel Muálem de Moraes Alves ◽  
Adriana Cunha Souza ◽  
Thaynara Parente de Carvalho ◽  
José Henrique Furtado Campos ◽  
...  

2016 ◽  
Vol 166 ◽  
pp. 21-28 ◽  
Author(s):  
Mariana C. Duarte ◽  
Grasiele S.V. Tavares ◽  
Diogo G. Valadares ◽  
Daniela P. Lage ◽  
Tatiana G. Ribeiro ◽  
...  

2021 ◽  
Vol 5 (1) ◽  
pp. 44
Author(s):  
Tavane Aparecida Alvarenga ◽  
Osvaine Júnior Alvarenga Alves ◽  
Mariana Cintra Pagotti ◽  
Wilson Roberto Cunha ◽  
Márcio Luís Andrade e Silva ◽  
...  

This study analyzes the antileishmanial activity of the crude ethanol extract, fractions, and isolated compounds of A. othonianum nuts. Antileishmanial activity was evaluated against Leishmania amazonensis promastigotes in vitro. The phytochemical study was performed by high-performance liquid chromatography-high-resolution mass spectrometry-diode array detector (HPLC-HRMS-DAD) and by preparative HPLC. HPLC-HRMS-DAD analysis of the bioactive extract confirmed the presence of ten alkyl phenol derivatives that had previously been isolated from A. occidentale. Bioassay-guided isolation afforded cardanol triene, cardanol diene, cardanol monoene, cardol triene, anacardic acid triene, anacardic acid diene, and anacardic acid monoene. Cardol triene gave an IC50 of 80.66 µM. The obtained data suggest that the evaluated extract, fractions, and cardol triene had moderate activity against L. amazonensis promastigotes. This is the first description of alkyl phenols in A. othonianum.


2017 ◽  
Vol 127 ◽  
pp. 28-33 ◽  
Author(s):  
Claudia do Carmo Maquiaveli ◽  
Arina Lázaro Rochetti ◽  
Heidge Fukumasu ◽  
Paulo Cezar Vieira ◽  
Edson Roberto da Silva

Author(s):  
Raquel Regina Duarte Moreira ◽  
André Gonzaga dos Santos ◽  
Flavio Alexandre Carvalho ◽  
Caio Humberto Perego ◽  
Eduardo José Crevelin ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Amanda Louzano Moreira ◽  
Débora Botura Scariot ◽  
Bruna Luíza Pelegrini ◽  
Greisiele Lorena Pessini ◽  
Tânia Ueda-Nakamura ◽  
...  

Previous studies reported antiprotozoal activities of Sapindus saponaria L. The aim of this work was the evaluation of antileishmanial activity and mechanism of action of extract and fractions of S. saponaria L. Hydroethanolic extract (EHA) obtained from fruit pericarps was fractionated using solid-phase extraction in a reversed phase, resulting in fractions enriched with saponins (SAP fraction) and acyclic sesquiterpene oligoglycosides (OGSA fraction). The activities of EHA, SAP, and OGSA were evaluated by antiproliferative assays with promastigote and intracellular amastigote forms. Cytotoxicity on macrophages and hemolytic activity were also analyzed. Morphological and ultrastructural changes in Leishmania amazonensis promastigotes were evaluated by electron microscopy. Flow cytometry was used to investigate mitochondrial dysfunction and phosphatidylserine exposure. OGSA was more selective for parasites than mammalian J774A1 macrophage cells, with selectivity indices of 3.79 and 7.35, respectively. Our results showed that only the OGSA fraction did not present hemolytic activity at its IC50 for promastigote growth. Electron microscopy revealed changes in parasite flagellum, cell body shape, and organelle size, mainly mitochondria. Flow cytometry analysis indicated mitochondrial membrane and cell membrane dysfunction. OGSA showed antileishmanial activity, resulting in several changes to protozoa cells, including mitochondrial depolarization and early phosphatidylserine exposure, suggesting a possible apoptotic induction.


Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
A Crotti ◽  
F Dos Santos ◽  
L Magalhães ◽  
K Wakabayashi ◽  
G Aguiar ◽  
...  

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5741
Author(s):  
Thalita C. S. Ferreira ◽  
Ismael P. Sauter ◽  
Lina Borda-Samper ◽  
Enyd Bentivoglio ◽  
Jarina P. DaMata ◽  
...  

The dioctadecyldimethylammonium bromide (DODAB) is a double-chained cationic lipid with potent bactericide and fungistatic activities; however, its toxicity on protozoan parasites is still unknown. Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationary-phase promastigotes and amastigotes of Leishmania amazonensis, the causative agent of cutaneous leishmaniasis. Upon treatment with DODAB, we analyzed the parasite surface zeta-potential, parasite viability, cellular structural modifications, and intracellular proliferation. The DODAB cytotoxic effect was dose-dependent, with a median effective concentration (EC50) of 25 µM for both life-cycle stages, comparable to the reported data for bacteria and fungi. The treatment with DODAB changed the membrane zeta-potential from negative to positive, compromised the parasite’s morphology, affected the cell size regulation, caused a loss of intracellular organelles, and probably dysregulated the plasma membrane permeability without membrane disruption. Moreover, the parasites that survived after treatment induced small parasitophorous vacuoles and failed to proliferate inside macrophages. In conclusion, DODAB displayed antileishmanial activity, and it remains to be elucidated how DODAB acts on the protozoan membrane. Understanding this mechanism can provide insights into the development of new parasite-control strategies.


2019 ◽  
Vol 132 (6) ◽  
pp. jcs226183 ◽  
Author(s):  
Victor Soares Cavalcante-Costa ◽  
Mariana Costa-Reginaldo ◽  
Thamires Queiroz-Oliveira ◽  
Anny C. S. Oliveira ◽  
Natália Fernanda Couto ◽  
...  

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