**6. Conclusions**

Schistosomiasis is a neglected disease that is one of the most common chronic infections among the poorest people in the world. Most chemotherapeutic-based programs attempting to eradicate schistosomiasis in the developing world rely on the effectiveness of a single drug, praziquantel; therefore, there is an urgent need to identify new parasite targets and effective antischistosomal compounds. Secondary plant metabolites have attracted the attention of many researchers over the years as a result of the variety of their chemical structures and their broad range of biological activities that may provide lead structures for the development of new drugs. Recently, marine organisms have also been recognised as an attractive source of antiparasitic compounds, and it can be expected that other living organisms, such as insects and amphibians, will emerge as additional sources in the future. Discovering untapped natural sources of new anthelmintic compounds remains a major challenge and a source of novelty in the era of combinatorial chemistry and genomics. To find new anthelmintics, all sources of natural, synthetic and semi-synthetic lead compounds must be investigated. *In vitro* bioassays using parasitic worms have played a central role in the early pre-clinical stages of most research on potential natural anthelmintics. The identification of the antiplasmodial and antischistosomal activity of the sesquiterpene lactone artemisinin has stimulated interest in natural products, and soon, promising leads will be identified with new chemical types and active agents against schistosomiasis. Therefore, bioprospecting programmes related to the isolation of bioactive compounds must be rewarded, and the screening *in vitro* of chemical constituents belonging to different classes must be evaluated on the blood fluke *S. mansoni.*

The literature regarding antischistosomal compounds contains a large number of natural products screened for their schistosomicidal properties. However, only a few of these may be promising drug leads in the development of a therapeutic reserve for schistosomiasis. Therefore, it is important to continue to identify new drugs and to explore alternative strategies to improve screening efficacy. Most of the extracts or natural compounds were only evaluated with *in vitro* studies; it is expected that they will be evaluated using *in vivo* experimental models. Further, it must be mentioned that the results of *in vitro* assays with many drugs do not correspond to what is observed *in vivo*; however, *in vitro* screening could identify novel anthelmintics that could eventually translate into practical applications. Thus, while *in vitro* tests are recommended initially, the assessment of therapeutic activity using *in vivo* models should be performed.

The analysis of the *S. mansoni* genome and transcriptome offers great possibilities for identifying possible new drug targets and will facilitate further exploration of differences between host and parasite metabolic pathways. In addition to the isolation and structural determination of new drugs from natural products and information from the originating plant, the integration of the pharmacological properties of natural products with the functional genomic and proteomic studies in schistosome and *in vitro* screening methods with improved automatic high-content screening will be important tools to identify possible new drugs in the future and shed light on the approaches of helminth chemotherapy. Attempting new combinations of natural or synthetic drugs will be also important in discovering alternative drugs to replace the use of praziquantel.
