In this research project, we will implement a robust structure activity relationship SAR program aimed at the discovery and development of a new potent analog of the drug praziquantel (PZQ) for the treatment of schistosomiasis (bilharzia or 'snail fever'). It has been estimated that this parasitic disease infects over 200 million people with over 770 million people at risk in 70 countries. Unlike the drug development programs that are in place for other major global diseases, schistosomiasis suffers from a lack of new drug discovery. Also, PZQ is not a perfect drug due to it being preferentially effective against the adult parasite and less against the juvenile parasite. Because PZQ is the drug of choice for the treatment of schistosomiasis, there is the obvious risk of the establishment of drug resistance. Our objective is to design and develop novel diverse analogs of PZQ for optimization of their antischistosomal activity. This research will use a Rapid Parallel Synthesis (RPS) approach in the production of these analogs and then use a high-content assay to determine their effect on two stages of the schistosomes life cycle: adult and juvenile stages. The identification of a new potent praziquantel (PZQ) analog that is effective on both adult and juvenile parasites would greatly benefit many countries in their fight against schistosomiasis. In addition to helping combat the potential of drug resistance, a new analog could also be used as a probe to aid in the determination of the unknown mode of action of PZQ.
The aim of this research is to utilize a robust structure activity relationship SAR program towards the discovery of new praziquantel (PZQ) analogs for the treatment of schistosomiasis. These new analogs will be evaluated for their antischistosomal activity against adult and juvenile parasites. The optimized compounds will be useful to help combat the potential of drug resistance and for elucidating the mode of action of PZQ.