title: Altered sterol profile induced in Leishmania amazonensis by a natural dihydroxymethoxylated chalcone.
abstract: OBJECTIVE
  The effects of the antileishmanial chalcone 2',6'-dihydroxy-4'-methoxychalcone (DMC) on Leishmania amazonensis sterol composition and biosynthesis were investigated to obtain information about the mechanism of growth inhibition by DMC on this parasite.
  
  
  METHODS
  The interference of sterol biosynthesis by DMC was studied in drug-treated promastigotes by two different methods. (i) Newly synthesized sterols from parasites grown in the presence of [(3)H]mevalonate were analysed by thin layer chromatography (TLC)/fluorography. (ii) Total sterols extracted from the parasites grown with or without DMC were characterized by gas chromatography coupled to mass spectroscopy (GC/MS).
  
  
  RESULTS
  TLC and GC/MS analyses of sterols extracted from DMC-treated promastigotes revealed the accumulation of early precursors and a reduction in the levels of C-14 demethylated and C-24 alkylated sterols, as well as a reduction in exogenous cholesterol uptake.
  
  
  CONCLUSIONS
  This study demonstrates that the natural chalcone DMC alters the sterol composition of L. amazonensis and suggests that the parasite target is different from other known sterol inhibitors.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Eduardo Caio
authors.initials: EC
authors.lastname: Torres-Santos
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Sampaio-Santos
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Buckner
authors.forename: Kohei
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Michael
authors.initials: M
authors.lastname: Gelb
authors.forename: Julio A
authors.initials: JA
authors.lastname: Urbina
authors.forename: Bartira
authors.initials: B
authors.lastname: Rossi-Bergmann
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002599:Chalcone / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D007891:Leishmania / Q000737:chemistry / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis*
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D013261:Sterols; D002599:Chalcone