Temporal Aspects of Novel Thioredoxin Glutathione Reductase Inhibitors
Session Number
Project ID: MEDH 21
Advisor(s)
Dr. David L. Williams, Rush University
Discipline
Medical and Health Sciences
Start Date
17-4-2024 8:55 AM
End Date
17-4-2024 9:10 AM
Abstract
Despite being one of the most influential parasitic diseases in developing countries, schistosomiasis has historically been treated as an orphan disease. To date, one drug, praziquantel, exists for its treatment. However, praziquantel sees faults in its effects on juvenile worms and has been proven to be susceptible to developed resistance in schistosomes. Most current developments towards new treatment for schistosomiasis focus on the enzyme thioredoxin glutathione reductase (TGR) as a target, which is responsible for the majority of the parasite’s redox defenses. This enzyme is responsible for the reduction of both thioredoxin and glutathione, processes usually performed by distinct enzymes in mammals. Progress on developing a drug that targets TGR has produced several novel compounds. These compounds can be split into the categories of fast and slow inhibitors, with the former being active in vitro after 15 minutes of incubation and the latter taking upwards of 6 hours to show similar activity in vitro. In vivo, however, these slow inhibitors often act just as quickly or even more effectively than their fast counterparts. This paper attempts to address this inconsistency and utilize samples from schistosomes to create an environment in vitro to imitate this in vivo effect for ease of future testing.
Temporal Aspects of Novel Thioredoxin Glutathione Reductase Inhibitors
Despite being one of the most influential parasitic diseases in developing countries, schistosomiasis has historically been treated as an orphan disease. To date, one drug, praziquantel, exists for its treatment. However, praziquantel sees faults in its effects on juvenile worms and has been proven to be susceptible to developed resistance in schistosomes. Most current developments towards new treatment for schistosomiasis focus on the enzyme thioredoxin glutathione reductase (TGR) as a target, which is responsible for the majority of the parasite’s redox defenses. This enzyme is responsible for the reduction of both thioredoxin and glutathione, processes usually performed by distinct enzymes in mammals. Progress on developing a drug that targets TGR has produced several novel compounds. These compounds can be split into the categories of fast and slow inhibitors, with the former being active in vitro after 15 minutes of incubation and the latter taking upwards of 6 hours to show similar activity in vitro. In vivo, however, these slow inhibitors often act just as quickly or even more effectively than their fast counterparts. This paper attempts to address this inconsistency and utilize samples from schistosomes to create an environment in vitro to imitate this in vivo effect for ease of future testing.