Antischistosomal tetrahydro-γ-carboline sulfonamides
Rongguo Ren1, Xiaofang Wang1, Derek A Leas1
1College of Pharmacy, University of Nebraska Medical Center, 986125 Nebraska Medical Center, Omaha, NE, United States.
Bioorganic & Medicinal Chemistry Letters
|January 15, 2022
Summary
Researchers identified novel tetrahydro-γ-carboline sulfonamides as potent antischistosomal agents. These compounds show promising activity against Schistosoma mansoni, offering a new therapeutic avenue.
Area of Science:
- Medicinal Chemistry
- Parasitology
- Drug Discovery
Background:
- Schistosomiasis remains a significant global health burden, necessitating new chemotypes for effective treatment.
- Existing antischistosomal drugs face challenges including resistance and side effects, driving the search for novel therapeutic agents.
Purpose of the Study:
- To discover and characterize a new class of compounds with antischistosomal activity.
- To explore the structure-activity relationships of tetrahydro-γ-carboline sulfonamides against Schistosoma mansoni.
Main Methods:
- Synthesis and chemical characterization of tetrahydro-γ-carboline sulfonamide derivatives.
- Evaluation of antischistosomal activity using ex vivo assays against Schistosoma mansoni.
- Assessment of the impact of structural modifications on compound efficacy, solubility, and metabolic stability.
Main Results:
- Tetrahydro-γ-carboline sulfonamides represent a novel chemotype with significant antischistosomal properties.
- Both aryl sulfonamide and tetrahydro-γ-carboline moieties are crucial for high antischistosomal activity.
- Optimizing polarity for solubility and stability led to a decrease in antischistosomal efficacy.
- Two compounds demonstrated potent activity with IC50 values below 5 µM against ex vivo Schistosoma mansoni.
Conclusions:
- Tetrahydro-γ-carboline sulfonamides are a promising new class of antischistosomal drug candidates.
- Further optimization is needed to balance efficacy with favorable pharmacokinetic properties.
- This discovery opens new avenues for developing urgently needed treatments for schistosomiasis.
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