Antischistosomal Agents: State of Art and Perspectives

Abstract

Praziquantel has remained the drug of choice for schistosomiasis chemotherapy for almost 40 years. The pressing need to develop a new antischistosomal drug may necessitate exploring and filtering chemotherapeutic history to search for the most promising ones. In this context, this review attempts to summarize all progress made in schistosomiasis chemotherapy from the early 20th century (mid-1910s) to 2016. We gathered almost 100 compounds providing information on therapeutic action, specifically covering at least first in vivo studies in animal model and in vitro. Pharmacokinetic and toxicity profiles of antischistosomal agents were also described. Preclinical studies indicate a handful of promising future candidates.

In Vitro and in Vivo Antischistosomal Activities of Chalcones

“…Several natural and synthetic compounds have been evaluated against schistosomes in the last few years. [3] Among natural substances, chalcones constitute a class that displays a wide spectrum of biological activities, [12,13] including their actions against parasites that cause neglected tropical diseases. [7,8] First, chalcones 1-15 were synthesized (Scheme 1) following the Claisen-Schmidt condensation reaction.…”

“…[15] Also, the tegument has key role in the protection of schistosome against the host immune system, being the major interface between its external environment. [3] Because of its importance to schistosomes survival, the tegument is the major target for the development of antischistosomal drugs. [3] Afterwards, we analyzed the in vivo schistosomicidal effects of chalcones 1 and 3 in a mouse model of schistosomiasis.…”

“…[3] Because of its importance to schistosomes survival, the tegument is the major target for the development of antischistosomal drugs. [3] Afterwards, we analyzed the in vivo schistosomicidal effects of chalcones 1 and 3 in a mouse model of schistosomiasis. As presented in Figures 3 and 4, there were significant reductions (P < 0.05) in worm burden upon oral treatment with 1 and 3 to mice after 49 days of post-infection.…”

“…[1 -3] In contrast, there are no availability of vaccines to schistosomiasis and its chemotherapy is dependent on praziquantel (PZQ), which does not act on immature worms and is the only drug in the market. [3,4] In addition, the reliance on a single schistosomicidal drug, as well as the emergence of worm strains less sensitive to PZQ, have raised the urgent need for new therapeutic antischistosomal drugs. [3 -6] In this context, chalcones (1,3-diaryl-2-propen-1ones) are natural plant metabolites that display antiparasitic activities against Leishmania, Trypanosoma, and Plasmodium species.…”

Chemotherapy for Fighting Schistosomiasis: Past, Present and Future

“… Chemical structures of artemether ( 59 ), artesunate ( 60 ), artemisone ( 61 ), and arterolane ( 62 ) …”