title: Effects of (-) mammea A/BB isolated from Calophyllum brasiliense leaves and derivatives on mitochondrial membrane of Leishmania amazonensis.
abstract: We have previously demonstrated antileishmanial activity on Leishmania amazonensis of the natural (1-2), synthetic (7) and derivatives of coumarin (-) mammea A/BB (3-6) isolated from the dichloromethane extract of Calophyllum brasiliense leaves. The aim of the present study was to evaluate morphological and ultrastructural alterations in Leishmania amazonensis induced by these compounds. In promastigote forms, all seven compounds produced significant morphological and ultrastructural alterations, as revealed by scanning and transmission electron microscopy. The compound 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one (3), the most active antileishmanial with LD₅₀ of 0.9 μM), induced cell shrinkage and a rounded appearance of the cells. Parasites incubated in the presence of compound (3) showed ultrastructural changes, such as the appearance of mitochondrial swelling with a reduction in the density of the mitochondrial matrix and the presence of vesicles inside the mitochondrion, indicating damage and significant change in this organelle; abnormal chromatin condensation, alterations in the nuclear envelope, intense atypical cytoplasmic vacuolization, and the appearance of autophagic vacuoles were also observed. In addition, the compound (3) may be acting to depolarize the mitochondrial membrane potential of the cells, leading to death of the parasite.
authors.affiliation: Pós-doutoranda em Ciências Farmacêuticas, Departamento de Farmácia e Farmacologia, Universidade Estadual de Maringá, Av. Colombo 5790, 87020-900 Maringá, PR, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Brenzan
authors.forename: A O
authors.initials: AO
authors.lastname: Santos
authors.forename: C V
authors.initials: CV
authors.lastname: Nakamura
authors.forename: B P Dias
authors.initials: BP
authors.lastname: Filho
authors.forename: T
authors.initials: T
authors.lastname: Ueda-Nakamura
authors.forename: M C M
authors.initials: MC
authors.lastname: Young
authors.forename: A G
authors.initials: AG
authors.lastname: Côrrea
authors.forename: J Alvim
authors.initials: JA
authors.lastname: Júnior
authors.forename: J A
authors.initials: JA
authors.lastname: Morgado-Díaz
authors.forename: D A G
authors.initials: DA
authors.lastname: Cortez
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029759:Calophyllum / Q000737:chemistry*; D002839:Chromans / Q000302:isolation & purification / Q000494:pharmacology; D002843:Chromatin / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry*; D005434:Flow Cytometry; D020128:Inhibitory Concentration 50; D007894:Leishmania mexicana / Q000187:drug effects* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000187:drug effects*; D009685:Nuclear Envelope / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*
chemical_list: C572384:5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one; D000981:Antiprotozoal Agents; D002839:Chromans; D002843:Chromatin; D003374:Coumarins; D010936:Plant Extracts