title: Definition of an electronic profile of compounds with inhibitory activity against hematin aggregation in malaria parasite.
abstract: Malaria is one of the most important parasitic diseases, affecting almost half of the world and posing a threat to the other half. Xanthone derivatives can behave as antimalarial drugs in the same mechanistic way as chloroquine and other related quinolines. This action is due to the inhibition of the detoxification pathway of the parasite, responsible for the production of hemozoin. We report a study of the electronic properties of the xanthonic and quinolinic compounds based on DFT calculations, in order to determine a pattern that could be applied to the development of new potentially active antimalarial molecules. As a result, a new interpretation of structure-activity relationship of the quinoline antimalarial drugs, and of the active hydroxylated xanthones is proposed here. We conclude that electronic features rather than steric factors control primarily the inhibitory activity of the studied compounds against hematin aggregation, concurring to a potential antimalarial activity.
authors.affiliation: Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto, Faculdade de Farmácia, Rua Aníbal Cunha, 164 4050-047 Porto, Portugal.
authors.forename: César
authors.initials: C
authors.lastname: Portela
authors.forename: Carlos M M
authors.initials: CM
authors.lastname: Afonso
authors.forename: Madalena M M
authors.initials: MM
authors.lastname: Pinto
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Ramos
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D006427:Hemin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000469:parasitology*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D055672:Static Electricity; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D044004:Xanthones; D006427:Hemin; C009689:xanthone