In vitro schistosomicidal activity of Usnea steineri extract and its major constituent (+)-usnic acid against Schistosoma mansoni

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

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Faculty Opinions recommendation of Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1018413.209475 ◽

2004 ◽

Author(s):

Paul J Brindley

Keyword(s):

Schistosoma Mansoni ◽

Praziquantel Treatment

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In Vitro Synergistic Interaction Between Amide Piplartine and Antimicrobial Peptide Dermaseptin Against Schistosoma mansoni Schistosomula and Adult Worms

Current Medicinal Chemistry ◽

10.2174/0929867311320020010 ◽

2012 ◽

Vol 20 (2) ◽

pp. 301-309 ◽

Cited By ~ 1

Author(s):

J. de Moraes ◽

J. Keiser ◽

K. Ingram ◽

C. Nascimento ◽

L.F. Yamaguchi ◽

...

Keyword(s):

Antimicrobial Peptide ◽

Schistosoma Mansoni ◽

Synergistic Interaction

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Biological and In silico Studies on Synthetic Analogues of Tyrosine Betaine as Inhibitors of Neprilysin - A Drug Target for the Treatment of Heart Failure

Current Pharmaceutical Design ◽

10.2174/1381612824666180515114236 ◽

2018 ◽

Vol 24 (17) ◽

pp. 1899-1904

Author(s):

Daniel Fabio Kawano ◽

Marcelo Rodrigues de Carvalho ◽

Mauricio Ferreira Marcondes Machado ◽

Adriana Karaoglanovic Carmona ◽

Gilberto Ubida Leite Braga ◽

...

Keyword(s):

Heart Failure ◽

Secondary Metabolites ◽

Structural Similarity ◽

Structural Features ◽

Major Constituent ◽

Binding Modes ◽

Starting Point ◽

In Silico Studies ◽

Nep Inhibition

Background: Fungal secondary metabolites are important sources for the discovery of new pharmaceuticals, as exemplified by penicillin, lovastatin and cyclosporine. Searching for secondary metabolites of the fungi Metarhizium spp., we previously identified tyrosine betaine as a major constituent. Methods: Because of the structural similarity with other inhibitors of neprilysin (NEP), an enzyme explored for the treatment of heart failure, we devised the synthesis of tyrosine betaine and three analogues to be subjected to in vitro NEP inhibition assays and to molecular modeling studies. Results: In spite of the similar binding modes with other NEP inhibitors, these compounds only displayed moderate inhibitory activities (IC50 ranging from 170.0 to 52.9 µM). However, they enclose structural features required to hinder passive blood brain barrier permeation (BBB). Conclusions: Tyrosine betaine remains as a starting point for the development of NEP inhibitors because of the low probability of BBB permeation and, consequently, of NEP inhibition at the Central Nervous System, which is associated to an increment in the Aβ levels and, accordingly, with a higher risk for the onset of Alzheimer's disease.

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Chemical Composition and in-vitro antimicrobial screening of leaf essential oil of Plectranthus gerardianus Benth., and isolation of the major constituent of oil

The Natural Products Journal ◽

10.2174/2210315510999200731183701 ◽

2020 ◽

Vol 10 ◽

Author(s):

Navadha Bhatt ◽

Navabha Joshi ◽

Kapil Ghai ◽

Om Prakash

Keyword(s):

Antimicrobial Activity ◽

Essential Oil ◽

Major Constituent ◽

In Vitro Antimicrobial Activity ◽

Gram Positive Bacteria ◽

Medicinal Value ◽

Leaf Essential Oil ◽

Plant Families ◽

Total Oil

Background: The Lamiaceae (Labiatae) is one of the most diverse and widespread plant families’ in terms of ethno medicine and its medicinal value is based on the volatile oils concentration. This family is important for flavour, fragrance and medicinal properties. Manyplants belonging to this family have indigenous value. Method: The essential oil of Plectranthus gerardianusBenth. (Lamiaceae), was analysed by GC and GC-MS analysis, while the major component was isolated and conformed by NMR spectroscopy. Result: The oil was found to be rich in oxygenated monoterpenes, which contribute around 62% of the total oil. The major components identified were fenchone (22.90%) and carvenone oxide (16.75%), besides other mono and sesquiterpenoids. The in-vitro antimicrobial activity of essential oil was tested against three gram negative bacteria viz. Pasteurellamultocida, Escherichia coli, and Salmonella enterica, two gram positive bacteria viz. Staphylococcus aureus and Bacillus subtilis and two fungi viz. Candida albicans and Aspergillusflavus. The antimicrobial activity of the oil was also compared to the antimicrobial activity of leaf essential oil of another Himalayan plant viz. Nepetacoerulescens. Conclusion: The oil showed in-vitro antimicrobial activity against all the microbial strains and can lessen the ever-growing demand of potentially hazardous antibiotics for treatment.

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Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

Pharmaceuticals ◽

10.3390/ph14070686 ◽

2021 ◽

Vol 14 (7) ◽

pp. 686

Author(s):

Raquel Porto ◽

Ana C. Mengarda ◽

Rayssa A. Cajas ◽

Maria C. Salvadori ◽

Fernanda S. Teixeira ◽

...

Keyword(s):

Schistosoma Mansoni ◽

Screening Strategy ◽

Early Infection ◽

Global Public Health ◽

Parasitic Worm ◽

Electron Microscopy Analysis ◽

Health Significance ◽

Microscopy Analysis

The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.

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