epiisopiloturine and imidazole

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

Topics: 4-Butyrolactone; Alkaloids; Animals; Anthelmintics; Anti-Bacterial Agents; Imidazoles; Pilocarpus; Plant Extracts; Plant Leaves; Vero Cells

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.

Topics: 4-Butyrolactone; Animals; Chlorocebus aethiops; Imidazoles; Mice; Pilocarpus; Reproduction; Schistosoma mansoni; Vero Cells