Date of Award
1-2026
Document Type
Thesis
Degree Name
Master of Science (MS)
College/School
College of Science and Mathematics
Department/Program
Chemistry and Biochemistry
Thesis Sponsor/Dissertation Chair/Project Chair
Nina Goodey
Committee Member
David Rotella
Committee Member
Kathleen Frey
Abstract
Lymphatic filariasis is a neglected tropical disease that impacts nearly 120 million people worldwide. The majority of individuals suffering from this disease are infected with parasitic worms, Wuchereria bancrofti (Wb) causing 90% of cases. These parasitic worms are transmitted through mosquito vectors, resulting in the invasion and colonization of the host's lymphatic system. Medications that are currently available have many off-target effects, which emphasizes the importance of discovering an innovative approach for targeted treatments. We hypothesize that dihydrofolate reductase (DHFR) is a promising therapeutic target for treating lymphatic filariasis due to its essential role in folate metabolism and nucleotide biosynthesis. Evaluating WbDHFR as a potential drug target requires a comprehensive assessment of its enzymatic function, including the rate-limiting step and its interactions with both established and prospective antifolate compounds. The catalytic mechanism of WbDHFR was investigated by conducting multiple turn-over pH profiles, solvent viscosity effects under multiple and single turn-over conditions with glycerol, kinetic isotope effects with deuterium, and the association and dissociation of methotrexate. Additionally, to assess the potency of various antifolate compounds such as methotrexate, TSD001, TSD10, TSD25, Oligo2, Oligo3a, Oligo3b and Oligo5, were tested and analyzed utilizing IC₅₀ plots and/or Ki determination. The results from these experiments can provide critical insight into WbDHFR’s catalytic pathway and inhibitor interactions, leading to the potential development of more selective antifolates.
File Format
Recommended Citation
Wilhelm, Jacquelyn J., "Inhibition and Kinetic Characterization of Wuchereria bancrofti Dihydrofolate Reductase, A Potential Lymphatic Filariasis Drug Target" (2026). Theses, Dissertations and Culminating Projects. 1628.
https://digitalcommons.montclair.edu/etd/1628