title: Synthesis and aromatase inhibitory activity of flavanones.
abstract: OBJECTIVE
  Aromatase inhibitors are known to prevent the conversion of androgens to estrogens and play a significant role in the treatment of estrogen dependent diseases such as breast cancer. Some flavonoids have been reported as potent aromatase inhibitors; therefore, in an effort to develop novel anti breast cancer agents, B ring substituted flavanones with a 7-methoxy group on A ring were synthesized and tested to assess their ability to inhibit aromatase activity and to determine the optimal B ring substitution pattern.
  
  
  METHODS
  A series of flavanones was prepared by cyclisation of 2'-hydroxychalcones previously obtained by Claisen-Schmidt condensation and the aromatase inhibitory activity of these compounds was investigated using human placental microsomes and radiolabeled [1,2,6,7-(3)H]-androstenedione as substrate.
  
  
  RESULTS
  Almost all flavanones exhibited inhibitory effect on the aromatase activity but their potency was dependent on their B ring substitution pattern. Hydroxylation at position 3' and/or 4' enhanced the anti-aromatase activity; thus, 3',4'-dihydroxy-7-methoxyflavanone was found to be twice more potent than aminoglutethimide, the first aromatase inhibitor clinically used.
  
  
  CONCLUSIONS
  These results indicated that these flavanones could be considered as potential anti breast cancer agents through the inhibition of aromatase activity and allowed us to select some of these compounds as skeleton for the development of flavonoid structurally-related aromatase inhibitors.
authors.affiliation: UPRES EA 1085, Biomolécules et Cibles Cellulaires Tumorales-Prolifération cellulaire et inhibition enzymatique Faculté de Pharmacie, Limoges, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Pouget
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagnere
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Basly
authors.forename: Anne-Elise
authors.initials: AE
authors.lastname: Besson
authors.forename: Yves
authors.initials: Y
authors.lastname: Champavier
authors.forename: Gerard
authors.initials: G
authors.lastname: Habrioux
authors.forename: Albert-Jose
authors.initials: AJ
authors.lastname: Chulia
mesh_terms: D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology
chemical_list: D047072:Aromatase Inhibitors; D005419:Flavonoids; D001141:Aromatase