Structural parameters, molecular properties, and biological evaluation of some terpenes targeting Schistosoma mansoni parasite

Mafud, Ana Carolina; Silva, Marco P. N.; Monteiro, Daniela C.; Oliveira, Maria Fátima; Resende, João G.; Coêlho, Mayara Ladeira; Sousa, Damião Pergentino de; Mendonça, Ronaldo Zucatelli; Pinto, Pedro; Freitas, Rivelilson Mendes de; Mascarenhas, Yvonne P.; Moraes, Josué de

doi:10.1016/j.cbi.2015.12.003

Cited by 40 publications

(23 citation statements)

References 34 publications

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“…The anthelmintic effect of the alkaloid EPIIS was 100 times greater than that reported previously where the effect of the alkaloid EPI against S. mansoni was found to be 300 μg mL −1 (Veras et al ., ). Antischistosomal activity has been described in the literature for various isolated molecules: the monoterpenes carvacryl acetate at ~30 μM (de Moraes et al ., ), 3,7‐dimethyl‐1‐octanol at ~20 μM (Mafud et al , ) and (+)− limonene epoxide at ~165 μM (de Moraes et al ., ); the sesquiterpene nerolidol at ~30 μM (Silva et al , ); the diterpene alcohol phytol at ~170 μM (de Moraes et al , ); the alkaloids piperamide 1 at ~170 μM (Carrara et al , ) and piplartine at ~10 μM (Moraes et al , ; de Moraes et al , ); the chalcone cardamonin at ~25 (de Castro et al , ); and for the cationic antimicrobial peptide dermaseptin 01 at ~15 μM (de Moraes et al ., ). In comparison with these results, the alkaloid EPIIS at only 3.125 μg mL −1 (~10 μM) showed a strong effect against S. mansoni , and further investigation of this molecule as an anthelmintic agent is clearly desirable.…”

Section: Resultsmentioning

confidence: 99%

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

et al. 2017

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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.

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Section: Resultsmentioning

confidence: 99%

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

et al. 2017

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“…All the adult worms recovered were incubated in RPMI medium supplemented with 10% FBS containing antibiotics at 37°C in a 5% CO 2 atmosphere. In preparation for in vitro biological assays, all compounds were solubilized in DMSO (30).…”

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

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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.

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“…Structure-activity relationship (SAR) is often used in QSAR-based studies as there is a correlation between the molecular structure of a compound and its biological activity (Mafud et al, 2016). In the present study, we used PaDEL, an open-source software for calculating various descriptors of peptides (Yap, 2011).…”

Section: Chemical Descriptorsmentioning

confidence: 99%

A Method for Predicting Hemolytic Potency of Chemically Modified Peptides From Its Structure

Kumar

Agrawal

et al. 2020

Front. Pharmacol.

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In the present study, a systematic effort has been made to predict the hemolytic potency of chemically modified peptides. All models have been trained, tested, and evaluated on a dataset that contains 583 modified hemolytic peptides and a balanced number of nonhemolytic peptides. Machine learning techniques have been used to build the classification models using an immense range of peptide features that include 2D, 3D descriptors, fingerprints, atom, and diatom compositions. Random Forest based model developed using fingerprints as an input feature achieved maximum accuracy of 78.33% with AUC of 0.86 on the main dataset and accuracy of 78.29% with AUC of 0.85 on the validation dataset. Models developed in this study have been incorporated in a web server "HemoPImod" to facilitate the scientific community (http://webs.iiitd.edu.in/raghava/ hemopimod/).

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Structural parameters, molecular properties, and biological evaluation of some terpenes targeting Schistosoma mansoni parasite

Cited by 40 publications

References 34 publications

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

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

A Method for Predicting Hemolytic Potency of Chemically Modified Peptides From Its Structure

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