New 7,8-benzoflavanones as potent aromatase inhibitors: synthesis and biological evaluation.
Some natural compounds such as flavonoids are known to possess a moderate inhibitory activity against aromatase, this enzyme being an interesting target for hormone-dependent breast cancer treatment. It has been demonstrated that the modulation of flavonoid skeleton could increase anti-aromatase effect. Therefore, new 7,8-benzoflavanones were synthesized and tested for their activity toward aromatase inhibition. It was observed that the introduction of a benzo ring at position C-7 and C-8 on flavanone skeleton led to new potent aromatase inhibitors, the resulting 7,8-benzoflavanones being until nine times more potent than aminogluthetimide (the first aromatase inhibitor used clinically).
Yahiaoui
Samir
S
UPRES EA 4021 Biomolécules et Thérapies anti-tumorales, Faculté de Pharmacie, 2 rue du Docteur Marcland, 87025 Limoges cedex, France.
Fagnere
Catherine
C
Pouget
Christelle
C
Buxeraud
Jacques
J
Chulia
Albert-José
AJ
D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001554:Benzene / Q000737:chemistry*; D003500:Cyclization; D044950:Flavanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D000077289:Letrozole; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry
D047072:Aromatase Inhibitors; D044950:Flavanones; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole; D001554:Benzene; C028610:flavanone