title: Recent developments in trans-sialidase inhibitors of Trypanosoma cruzi.
abstract: Chagas is a lethal chronic disease that currently affects 8-10 million people worldwide, primarily in South and Central America. Trypanosoma cruzi trans-sialidase is an enzyme that is of vital importance for the survival of the parasite due to its key role in the transfer of sialic acid from the host to the parasite surface and it also helps the parasite combat the host's immune system. This enzyme has no equivalent human enzyme; thus, it has become an interesting target for the development of inhibitors that combat the parasite. In this review, we summarize three classes of inhibitors (acceptor, donor and unrelated) with their inhibition values and their mode of action against this enzyme. Based on molecular docking, molecular dynamics and structure-activity relationship studies, it has been discovered that the molecules with -NH2, -OH and -COOH groups on an aromatic ring could be used as a scaffold for the development of new and potent trans-sialidase inhibitors due to their key interaction with active enzyme sites. In particular, carboxylic acid derivatives have importance over the sugar moiety due to their ease of synthesis and unique structure-activity relationship.
authors.affiliation: a Centro de Biotecnología Genómica , Instituto Politécnico Nacional , Reynosa , Mexico.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Kashif
authors.affiliation: a Centro de Biotecnología Genómica , Instituto Politécnico Nacional , Reynosa , Mexico.
authors.forename: Antonio
authors.initials: A
authors.lastname: Moreno-Herrera
authors.affiliation: a Centro de Biotecnología Genómica , Instituto Politécnico Nacional , Reynosa , Mexico.
authors.forename: Edgar E
authors.initials: EE
authors.lastname: Lara-Ramirez
authors.affiliation: b Escuela Nacional de Medicina y Homeopatía , Instituto Politécnico Nacional , Ciudad de Mexico , Mexico.
authors.forename: Esther
authors.initials: E
authors.lastname: Ramírez-Moreno
authors.affiliation: a Centro de Biotecnología Genómica , Instituto Politécnico Nacional , Reynosa , Mexico.
authors.forename: Virgilio
authors.initials: V
authors.lastname: Bocanegra-García
authors.affiliation: c Department of Chemistry , The Islamia University of Bahawalpur , Bahawalpur , Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashfaq
authors.affiliation: a Centro de Biotecnología Genómica , Instituto Politécnico Nacional , Reynosa , Mexico.
authors.forename: Gildardo
authors.initials: G
authors.lastname: Rivera
mesh_terms: D000818:Animals; D001665:Binding Sites; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D062105:Molecular Docking Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D006023:Glycoproteins; D014344:Trypanocidal Agents; C069715:trans-sialidase; D009439:Neuraminidase
keywords: Trypanosoma cruzi; carboxylic acid; inhibitors; molecular docking; trans-sialidase