Activity of Epiisopiloturine Against Schistosoma mansoni

Abstract

Schistosomiasis, caused by blood flukes of the genus Schistosoma, still imposes a considerable public health burden on large parts of the world. The control of this disease depends almost exclusively on the drug praziquantel, and there are no alternative drugs in sight. Natural compounds have recently attracted significant attention due to their relevance to parasitic infection and potential development into new therapeutic agents. Epiisopiloturine is an imidazole alkaloid isolated from the leaves of Pilocarpus microphyllus (Rutaceae), a native plant from Brazil. Here, we report the in vitro effect of this drug on the survival time of Schistosoma mansoni of different ages, such as 3 h old and 1, 3, 5, and 7 days old schistosomula, 49-day-old adults, and on egg output by adult worms. Epiisopiloturine at a concentration of 300 μg/mL caused the death of all schistosomula within 120 h. Extensive tegumental alterations and death were observed when adult schistosomes had been exposed to 150 μg/mL of the epiisopiloturine. At the highest sub-lethal dose of alkaloid (100 μg/mL), a 100% reduction in egg laying of paired adult worms was observed. Additionally, epiisopiloturine showed selective antischistosomal activity and exhibited no cytotoxicity to mammalian cells. This report provides the first evidence that epiisopiloturine is able to kill S. mansoni of different ages and inhibit worm egg laying.

Effect of neem ( Azadirachta indica A. Juss) leaf extract on resistant Staphylococcus aureus biofilm formation and Schistosoma mansoni worms

“…Similar results were obtained by previous studies using other antischistosomal compounds, such as piplartine, dermaseptin and phytol de Moraes et al, 2011;de Moraes et al, 2014). The schistosomes tegument is an important target for antischistosomal drugs, alterations in the surface topography of worms were used by several studies for the evaluation of antischistosomal drugs activities in vitro and in vivo (Veras et al, 2012;Guimarães et al, 2014;de Moraes et al, 2014).…”

Natural Products with Antischistosomal Activity

“…Similar to piplartine (18), this alkaloid has shown in vitro schistosomicidal properties against schistosomula and adult S. mansoni worms [49,84]. However, the parasite mortality occurred at concentrations above 500 μM.…”

“…Alkaloids are widely distributed in nature and they have been isolated from several plant species [17,18]. Piplartine [62,63], piperamide 1 [61], epiisopiloturine [49,84], sanguinarine [64], solamargine and solasonine [68] are alkaloids with in vitro antischistosomal properties. Mefloquine, an aminoalcohol derived from quinine, has in vitro and in vivo schistosomicidal activity (Figure 2) [57,58].…”

“…Epiisopiloturine (20) is an imidazole alkaloid isolated from the leaves of Pilocarpus microphyllus (Rutaceae), a native plant from Brazil [49]. Similar to piplartine (18), this alkaloid has shown in vitro schistosomicidal properties against schistosomula and adult S. mansoni worms [49,84].…”

“…In addition, microscopic analysis revealed tegumental alterations when adult schistosomes had been exposed to epiisopiloturine. Despite the high concentration (>500 μM), epiisopiloturine showed selective antischistosomal activity and exhibited no cytotoxicity to mammalian cells [49]. Recently, an industrial scale process for extraction, purification and isolation of epiisopiloturine has been described [87].…”