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A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Trypanosoma cruzi Agents
Eyra Ortiz-Perez1, Domingo Mendez-Alvarez1, Alfredo Juarez-Saldivar2
1Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, México.
Medicinal Chemistry (Shariqah (United Arab Emirates))
|July 31, 2024
Summary
New drug discovery for Chagas disease is crucial as current treatments are ineffective. This study identified potent carbonic anhydrase inhibitors from sulfonamide derivatives with promising trypanocidal activity against Trypanosoma cruzi.
Area of Science:
- Medicinal Chemistry
- Parasitology
- Drug Discovery
Background:
- Chagas disease lacks effective treatments despite decades of research.
- Carbonic anhydrase of Trypanosoma cruzi (α-TcCA) is a validated target for novel antiparasitic drug design.
Purpose of the Study:
- To identify novel α-TcCA inhibitors with significant trypanocidal activity.
- To explore potential drug candidates for Chagas disease treatment.
Main Methods:
- Virtual screening using maximum common substructure (MCS) and molecular docking.
- In vitro evaluation against Trypanosoma cruzi NINOA strain.
- Cytotoxicity assessment in J774.2 macrophage cells.
Main Results:
- Five sulfonamide derivatives exhibited high docking scores (-6.94 to -8.31 kcal/mol) and interacted with α-TcCA active site residues.
- Compounds C7, C9, and C21 demonstrated potent in vitro activity against Trypanosoma cruzi epimastigotes with IC50 values of 26, 61.6, and 49 μM, respectively.
- Selected compounds displayed favorable biopharmaceutical and pharmacokinetic properties.
Conclusions:
- Compounds C7, C9, and C21 possess significant trypanocidal activity.
- The identified sulfonamide scaffold is a promising basis for developing new anti-Chagas disease agents.
