title: Leishmanicidal activity of benzophenones and extracts from Garcinia brasiliensis Mart. fruits.
abstract: Infections by protozoans of the genus Leishmania are the major worldwide health problem, with high endemicity in developing countries. The drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which exert renal and cardiac toxicity. Thus, there is a strong need for safer and more effective treatments against leishmaniasis. The present study was designated to evaluate, by a bioguided assay, the leishmanicidal activity of extracts (hexane, ethyl-acetate and ethanolic) and molecules both obtained by means of extraction from pericarps of Garcinia brasiliensis fruits. The hexane extract presented the best activity on the extracellular (promastigotes) and intracellular (amastigotes) forms of Leishmania (L.) amazonensis, when compared to the other extracts. Based on these findings, this extract was fractionated by silica gel column chromatography, affording nine fractions then resulting in three purified prenylated benzophenones - 7-epi-clusianone (1), garciniaphenone (2) and guttiferone-a (3). They showed significant activity on Leishmania (L.) amazonensis, and little toxicity for mammalian cells. Structure-activity relationships were evaluated showing that the IC(50) value displayed is dependent of prenyl groups and phenolic hydroxyls number, and inversely proportional to the hydrophobicity. Our results are promising, showing that these compounds are biologically active on Leishmania (L.) amazonensis.
authors.affiliation: Department of Pharmacy, Laboratory of Phytochemistry and Medicinal Chemistry, Federal University of Alfenas, MG, Brazil. ivan.farma@bol.com.br
authors.forename: I O
authors.initials: IO
authors.lastname: Pereira
authors.forename: M J
authors.initials: MJ
authors.lastname: Marques
authors.forename: A L R
authors.initials: AL
authors.lastname: Pavan
authors.forename: B S
authors.initials: BS
authors.lastname: Codonho
authors.forename: C L
authors.initials: CL
authors.lastname: Barbiéri
authors.forename: L A
authors.initials: LA
authors.lastname: Beijo
authors.forename: A C
authors.initials: AC
authors.lastname: Doriguetto
authors.forename: E C
authors.initials: EC
authors.lastname: D'Martin
authors.forename: M H
authors.initials: MH
authors.lastname: dos Santos
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001577:Benzophenones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D005638:Fruit; D029760:Garcinia / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy* / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000469:parasitology; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D000977:Antiparasitic Agents; D001577:Benzophenones; D010936:Plant Extracts