title: Cruzain inhibitors: efforts made, current leads and a structural outlook of new hits.
abstract: Human African trypanosomiasis and Chagas disease are the main causes of heart failure in developing countries. The disadvantages of current therapy include: undesirable side-effects, resistance, lack of efficacy on late-stage disease and lack of pediatric formulations. Efforts to find new compound hits have spanned SAR studies to very high-throughput and virtual screens and drug repurposing. The integrated analysis of these strategies on the discovery of anti-Chagas agents is timely. This work accounts for the progress on the development of cruzain inhibitors following these avenues, with emphasis on structural aspects of the ligand-cruzain recognition process.
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City 04510, Mexico. Electronic address: kmtzm@unam.mx.
authors.forename: Karina
authors.initials: K
authors.lastname: Martinez-Mayorga
authors.affiliation: The University of Alabama in Huntsville, Huntsville, AL 35899, USA.
authors.forename: Kendall G
authors.initials: KG
authors.lastname: Byler
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City 04510, Mexico.
authors.forename: Ariadna I
authors.initials: AI
authors.lastname: Ramirez-Hernandez
authors.affiliation: Instituto de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Mexico City 04510, Mexico.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Terrazas-Alvares
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000469:parasitology; D017076:Computer-Aided Design; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D057166:High-Throughput Screening Assays; D006801:Humans; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000201:enzymology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi