Efficacy of carvacryl acetate in vitro and following oral administration to mice harboring either prepatent or patent Schistosoma mansoni infections.

Schistosomiasis is a major public health problem that afflicts more than 240 million individuals globally, particularly in poor communities. Treatment of schistosomiasis relies heavily on a single oral drug, praziquantel, and there is interest in the search for new antischistosomal drugs. This study reports the anthelmintic evaluation of carvacryl acetate, a derivative of the terpene carvacrol, against Schistosoma mansoni ex vivo and in a schistosomiasis animal model harboring either adult (patent infection) or juvenile (prepatent infection) parasites. For comparison, data obtained with gold standard antischistosomal drug praziquantel are also presented. Initially in vitro effective concentrations of 50% (EC50) and 90% (EC90) were determined against larval and adult stages of S. mansoni. In an animal with patent infection, a single oral dose of carvacryl acetate (100, 200, or 400 mg/kg) caused a significant reduction in worm burden (30-40%). S. mansoni egg production, a process responsible for both life cycle and pathogenesis, was also markedly reduced (70-80%). Similar to praziquantel, carvacryl acetate 400 mg/kg had low efficacy in pre-patent infection. In tandem, although carvacryl acetate had interesting in vitro schistosomicidal activity, the compound exhibited low efficacy in terms of reduction of worm load in S. mansoni-infected mice.

Evaluation of Gibbilimbol B, Isolated from Piper malacophyllum (Piperaceae), as an Antischistosomal Agent.

Infections caused by parasitic worms impose a considerable worldwide health burden. One of the most impactful is schistosomiasis, a disease caused by blood-dwelling of the genus Schistosoma that affects more than 230 million people worldwide. Since praziquantel has also been extensively used to treat schistosomiasis and other parasitic flatworm infections, there is an urgent need to identify novel anthelmintic compounds, mainly from natural sources. In this study, the hexane extract from roots of Piper malacophyllum (Piperaceae) showed to be mainly composed for gibbilimbol B by HPLC/ESI-HRMS. Based on this result, this compound was isolated by chromatographic steps and its structure was confirmed by NMR. In vitro bioassays showed that gibbilimbol B was more active than praziquantel against larval stage of S. mansoni, with effective concentrations of 50 % (EC50 ) and 90 % (EC90 ) values of 2.6 and 3.4 µM, respectively. Importantly, gibbilimbol B showed no cytotoxicity to mammalian cells at a concentration 190 times greater than the antiparasitic effect, giving support for the anthelmintic potential of gibbilimbol B as lead compound for novel antischistosomal agents.

Phenotypic screening of nonsteroidal anti-inflammatory drugs identified mefenamic acid as a drug for the treatment of schistosomiasis.

BACKGROUND: Treatment and control of schistosomiasis, one of the most insidious and serious parasitic diseases, depend almost entirely on a single drug, praziquantel. Since the funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, 73 nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in medical and veterinary fields were evaluated for their anti-schistosomal properties. METHODS: The efficacy of NSAIDs was first tested against adult Schistosoma mansoni ex vivo using phenotypic screening strategy, effective drugs were further tested in a murine model of schistosomiasis. The disease parameters measured were worm and egg burden, hepato- and splenomegaly. FINDINGS: From 73 NSAIDs, five (mefenamic acid, tolfenamic acid, meclofenamic acid, celecoxib, and diclofenac) were identified to effectively kill schistosomes. These results were further supported by scanning electron microscopy analysis. In addition, the octanol-water partition coefficient, both for neutral and ionized species, revealed to be a critical property for the ex vivo activity profile. Compounds were then tested in vivo using both patent and a prepatent S. mansoni infection in a mouse model. The most effective NSAID was mefenamic acid, which highly reduced worm burden, egg production, and hepato- and splenomegaly. INTERPRETATION: The treatment regimen used in this study is within the range for which mefenamic acid has been used in clinical practice, thus, it is demonstrated the capacity of mefenamic acid to act as a potent anti-schistosomal agent suitable for clinical repurposing in the treatment of schistosomiasis.