Antischistosomal Activity of Oxindolimine-Metal Complexes

Moraes, Josué de; Dário, Bruno S.; Couto, Ricardo Alexandre Alves de; Pintó, Pedro; Ferreira, Ana Maria da Costa

doi:10.1128/aac.01371-15

Cited by 30 publications

(21 citation statements)

References 30 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, additional concentrations of selected drugs were tested (25, 12.5, 6.25, and 3.12 M). The halfmaximum lethal concentrations (i.e., the LC 50 s) for active compounds were calculated with GraphPad Prism software using sigmoid dose-response curves and the 95% confidence intervals as previously described (33,34). Each concentration was tested in triplicate, and experiments were performed at least three times.…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

Guerra

Silva

et al. 2019

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

Schistosomiasis is a parasitic flatworm disease that infects over 200 million people worldwide, especially in poor communities. Treatment and control of the disease rely on just one drug, praziquantel. Since funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, from a screening of 13 marketed diuretics, we identified that spironolactone, a potassium-sparing diuretic, had potent antischistosomal effects on Schistosoma mansoni in vitro and in vivo in a murine model of schistosomiasis. In vitro, spironolactone at low concentrations (<10 µM) is able to alter worm motor activity and the morphology of adult schistosomes, leading to parasitic death. In vivo, oral treatment with spironolactone at a single dose (400 mg/kg) or daily for five consecutive days (100 mg/kg/day) in mice harboring either patent or prepatent infections significantly reduced worm burden, egg production, and hepato- and splenomegaly (P < 0.05 to P < 0.001). Taken together, with the safety profile of spironolactone, supported by its potential to affect schistosomes, these results indicate that spironolactone could be a potential treatment for schistosomiasis and make it promising for repurposing.

show abstract

Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

Guerra

Silva

et al. 2019

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…After the drug treatment (120 h) or in case of death, parasites were fixed in FAA (formalin‐acetic acid‐alcohol solution) and examined with a confocal microscope (laser scanning microscope, LSM 510 META, Carl Zeiss, Standorf Göttingen, Vertrieb, Germany) (Moraes et al ., ). LC 50 values were calculated by fitting the data to a sigmoidal dose–response curve using the graphpad prism (version 5.0) software (Graphpad, San Diego, CA, USA) (De Moraes et al , ).…”

Section: Methodsmentioning

confidence: 99%

“…The assays of S. mansoni performed in vitro were made as described previously (Veras et al, 2013;de Moraes et al, 2015). Solutions of the alkaloids were prepared in dimethyl sulfoxide (DMSO) or ethanol (0.5% final concentration) and used at concentrations varying from 1.5625 to 500 μg mL À1 .…”

Section: Anthelmintic Assaymentioning

confidence: 99%

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

et al. 2017

Self Cite

View full text Add to dashboard Cite

Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

“…Significant differences were determined by one-way analysis of variance (ANOVA) and applying Tukey's test for multiple comparisons with a level of significance set at P < 0.05. IC 50 values were also calculated using sigmoid dose-response curves in aforementioned software [9]. …”

Section: Methodsmentioning

confidence: 99%

“…In this regard, the search for antiparasitic compounds from natural sources, especially medicinal plants, has intensified [2, 7–9]. Several plants of the family Asteraceae have shown promising in vitro schistosomicidal activity [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Flavonoids and Sesquiterpene Lactones from Artemisia absinthium and Tanacetum parthenium against Schistosoma mansoni Worms

Almeida

Carvalho

Gazolla

et al. 2016

Evidence-Based Complementary and Alternative Medicine

Self Cite

View full text Add to dashboard Cite

Human schistosomiasis, caused by trematode worms of the genus Schistosoma, is one of the most significant neglected tropical diseases, affecting more than 200 million individuals worldwide and praziquantel is the only available drug to treat this disease. Artemisia absinthium L. and Tanacetum parthenium L. are species popularly used as anthelmintics. We investigated the in vitro schistosomicidal activity of crude extracts of A. absinthium (AA) and T. parthenium (TP) and their isolated compounds. AA and TP, at 200 μg/mL, were active, causing 100% mortality of all adult worms. Chromatographic fractionation of AA leads to isolation of artemetin and hydroxypelenolide, while santin, apigenin, and parthenolide were isolated from TP. Artemetin, hydroxypelenolide, santin, and apigenin, at 100 μM, were inactive against adult worms. Parthenolide (12.5 to 100 μM) caused 100% mortality, tegumental alterations, and reduction of motor activity of all adult worms of S. mansoni, without affecting mammalian cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms. This report provides the first evidence for the in vitro activity of parthenolide against adult worms of S. mansoni, opening the route to further schistosomicidal studies with this compound.

show abstract

Antischistosomal Activity of Oxindolimine-Metal Complexes

Cited by 30 publications

References 30 publications

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

In Vitro and In Vivo Studies of Spironolactone as an Antischistosomal Drug Capable of Clinical Repurposing

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

Flavonoids and Sesquiterpene Lactones from Artemisia absinthium and Tanacetum parthenium against Schistosoma mansoni Worms

Contact Info

Product

Resources

About