Degree Type


Date of Award


Degree Name

Master of Science




Analytical Chemistry

First Advisor

Brett VanVeller


Ascariasis is a neglected tropical disease that is caused by the nematode parasite Ascaris. Ascaris infections have high morbidity, cause debilitating conditions and affect at least one-quarter of world’s population. With no effective vaccine available, the prophylaxis and treatment of ascariasis rely on a limited supply of anthelmintic drugs. The massive use of anthelmintics led to the selection of resistant parasites, which has incurred anthelmintic resistance in many parasite species. It is therefore important to identify new lead compounds for anthelmintic drugs or to enhance the potency of existing anthelmintics. To address this issue, I chose a recently characterized ligand-gated ion channel, ACR-16 on Ascaris suum, as my drug target and attempted to discover new therapeutic compounds targeting at Asu-ACR-16 receptor. I used two approaches of structure-based drug discovery that are arranged into individual chapters in my thesis. In Chapter 2, the receptor-based drug design was applied to perform virtual screening of a library of ligands into the potential binding sites of receptor structure. The hit candidates were then pharmacologically characterized on Asu-ACR-16 expressed in Xenopus laevis oocytes using two-electrode voltage clamp. In Chapter 3, the ligand-based drug design was applied to optimize the structure of nicotine, a known nAChR agonist, to identify more potent and efficacious Asu-ACR-16 agonists. In conclusion, we reported four novel allosteric modulators from virtual screening and several (S)-anabasine derivatives as highly potent Asu-ACR-16 agonists.


Copyright Owner

Fudan Zheng



File Format


File Size

152 pages