Discovery of Novel Inhibitors of Cruzain Cysteine Protease of Trypanosoma cruzi

• Published in: Current medicinal chemistry Vol. 31; no. 16; p. 2285
• Main Authors: Prates, João Lucas Bruno, Lopes, Juliana Romano, Chin, Chung Man, Ferreira, Elizabeth Igne, Dos Santos, Jean Leandro, Scarim, Cauê Benito
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2024
• Subjects: Chagas Disease - drug therapy; Cysteine Endopeptidases - metabolism; Cysteine Proteinase Inhibitors - chemistry; Cysteine Proteinase Inhibitors - metabolism; Cysteine Proteinase Inhibitors - pharmacology; Drug Discovery; Humans; Molecular Docking Simulation; Protozoan Proteins - antagonists & inhibitors; Protozoan Proteins - chemistry; Protozoan Proteins - metabolism; Trypanocidal Agents - chemistry; Trypanocidal Agents - pharmacology; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - enzymology; Cysteine proteases; Chagas disease; drug development; cruzain; T. cruzi; new compounds
• ISSN: 1875-533X
• DOI: 10.2174/0109298673254864230921090519

Chagas disease (CD) is a parasitic disease endemic in several developing countries. According to the World Health Organization, approximately 6-8 million people worldwide are inflicted by CD. The scarcity of new drugs, mainly for the chronic phase, is the main reason for treatment limitation in CD. Therefore, there is an urgent need to discover new targets for which new therapeutical agents could be developed. Cruzain cysteine protease (CCP) is a promising alternative because this enzyme exhibits pleiotropic effects by acting as a virulence factor, modulating host immune cells, and interacting with host cells. This systematic review was conducted to discover new compounds that act as cruzain inhibitors, and their effects were studied through enzymatic assays and molecular docking. Additionally, the advances and perspectives of these inhibitors are discussed. These findings are expected to contribute to medicinal chemistry in view of the design of new, safe, and efficacious inhibitors against CCP detected in the last decade (2013-2022) to provide scaffolds for further optimization, aiming toward the discovery of new drugs.