Schistosomiasis is one of the world’s major public health problems, and praziquantel is the only available drug to treat this notable
neglected disease. Drug combinations have been considered an important strategy for treatment of infectious diseases, which might
enhance therapeutic efficacy and delaying resistance. In this study, we have examined the in vitro activities of the amide piplartine and
the antimicrobial peptide dermaseptin 01 administered singly or in combination against Schistosoma mansoni of different ages including
3-hour-old and 7-day-old schistosomula and 49-day-old adult schistosomes as well as on egg output by adult worms. We calculated the
median lethal concentrations (LC50) of 7.87 and 17.99 μM on 49-day-old adults, 11.02 and 71.58 μM on 7-day-old schistosomula, and
70.87 and 98.42 μM on 3-hour-old schistosomula for piplartine and dermaseptin, respectively. Most Piplartine/dermaseptin combinations
showed synergistic effect, with combination index (CI) values less than 0.9 when S. mansoni adults or schistosomula were simultaneously
incubated with both drugs in vitro; synergy between these two compounds was also indicated using isobolograms. Additionally, we
observed alterations on the tegumental surface of schistosomula and adult schistosomes by means of laser scanning confocal microscopy.
Furthermore, egg laying of surviving worms was considerably more reduced when exposed to the piplartine/dermaseptin combinations
than each drug alone, and this inhibition was irreversible. This is the first report on the synergistic effect between piplartine and dermaseptin
against S. mansoni and opens the route to further studies (e.g. in vivo) to characterize this combination in greater detail.
Keywords: Schistosoma mansoni, piplartine, dermaseptin, schistosomiasis, schistosomicidal activity, combination chemotherapy, synergism, combination index, anthelmintic activity, parasitic disease, natural compounds, confocal laser scanning microscopy, helminth
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