title: Solid-state electrochemical assay of heme-binding molecules for screening of drugs with antimalarial potential.
abstract: The interaction between heme and ligands is the basis for a variety of tests aimed at the discovery of antiplasmodial molecules. Two electrochemical methods for the screening of molecules with potential antimalarial activity through heme-binding mechanism are described. The first method is applicable to lipophilic environment, by using solution phase electrochemistry in DMSO solutions of Fe(III)-heme plus the tested compounds at carbon electrodes. This method provides well-defined voltammetric signals, characteristic of the heme-ligand (L) interaction. The second method involves aqueous media at biological pH and the use of voltammetry of immobilized particles, by means of microparticulate films of the tested compounds immersed into Fe(III)-heme solutions with no need of prior incubation. These methodologies are applied to the testing of heme-binding activity in macromolecular level systems like hemoglobin, or much more complex mixtures like total blood, erythrocytes, or hemolyzed samples.
authors.affiliation: Departament de Química Analítica, Facultat de Química, Universitat de València, Dr. Moliner 50, 46100 Burjassot, Valencia, Spain. antonio.domenech@uv.es
authors.forename: Antonio
authors.initials: A
authors.lastname: Doménech-Carbó
authors.forename: Alexandre
authors.initials: A
authors.lastname: Maciuk
authors.forename: Bruno
authors.initials: B
authors.lastname: Figadère
authors.forename: Erwan
authors.initials: E
authors.lastname: Poupon
authors.forename: Gerardo
authors.initials: G
authors.lastname: Cebrián-Torrejón
mesh_terms: D000962:Antimalarials / Q000032:analysis* / Q000737:chemistry; D037621:Artemisinins / Q000032:analysis* / Q000737:chemistry; D002244:Carbon; D002457:Cell Extracts / Q000737:chemistry; D055808:Drug Discovery; D055664:Electrochemical Techniques / Q000379:methods*; D004566:Electrodes; D004912:Erythrocytes / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D010084:Oxidation-Reduction; D011223:Praziquantel / Q000032:analysis* / Q000737:chemistry; D011803:Quinine / Q000032:analysis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D002457:Cell Extracts; D005290:Ferric Compounds; D006454:Hemoglobins; D008024:Ligands; D006418:Heme; D011223:Praziquantel; D002244:Carbon; C031327:artemisinin; D011803:Quinine