title: Therapeutic Approaches Blocking Glycan Synthesis as Targeting Strategy for Malaria.
abstract: Over one million people die from malaria each year, mainly in the world's tropical and sub-tropical areas. Several research efforts have been devoted to the design of new therapeutic targets for disease control, as drug resistance is one of the greatest challenges in malaria eradication. Carbohydrate recognition in Plasmodium-host interactions is one area for potential targets against disease. The glycan derivatives interfere with replication and invasion of Plasmodium falciparum. Sulfated glycosaminoglycans (GAGs) are known to block merozoite and sporozoite invasion. Heparin is a GAG that has been shown blocking the invasion by binding to the specific domain of merozoites surface (MSP) termed MSP-1. Although MSP does not bind to heparin-like GAG oligosaccharides, its ability to bind to small molecules has not yet been investigated. Besides this, the red blood cell also has glycans on the surface that mediate parasites-cell and cell-cell interactions. In this review, we aim to discuss drug mechanisms that act in carbohydrate synthesis targets in malaria disease.
authors.affiliation: Departamento de Imunologia, Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Pollyanna S
authors.initials: PS
authors.lastname: Gomes
authors.affiliation: Instituto de Microbiologia, Universidade Federal do Rio de Janeiro (UFRJ), CCS - Sala D1-035, Av. Carlos Chagas Filho, 373 - Cidade Universitária, CEP 21.941-902, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morrot
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D055808:Drug Discovery; D004351:Drug Resistance; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology; D054884:Host-Pathogen Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011134:Polysaccharides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D000962:Antimalarials; D020066:Merozoite Surface Protein 1; D011134:Polysaccharides
keywords: Malaria; antimalarials; carbohydrates target; drug-resistance; glycobiology; parasite-host interactions; pathogenesis