Document Type

Honors Project

Publication Date

6-13-2025

Abstract

chistosomiasis is a deadly and debilitating parasitic disease caused by Schistosoma mansoni which affects 200+ million people annually who come into contact with contaminated water. Currently only one drug (Praziquantel) has been used to treat this disease for almost 50 years, and fear of resistance is growing, thus a new drug and new target is needed. Inhibition of the organism-specific redox defense protein Thioredoxin Glutathione Reductase (TGR) has lead to the death of the worm in vitro, indicating that it would be a good druggable target. Fragment based analysis and x-ray crystallography have returned the outline of a lead compound which was analyzed, pieced apart, and optimized in silico using SwissDock and SwissADME to predict binding affinity and drug-like qualities. Synthesis work was done along two pathways: pyrroles and furans. Pyrroles employed a Paal-Knorr cyclization, Vilsmeier Haack formylation, and reductive amination. The furans consisted of a Meerwein arylation and reductive amination reaction. An in vitro assay against a human cell line was performed to determine potential harm in order to ensure the safety of the potential drugs for humans. Through in silico and in vitro work, the effectiveness of the compounds has been predicted and has informed the optimization of the lead compound for future work.

Level of Honors

magna cum laude

Department

Chemistry

Advisor

Stefan Debbert

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