A novel activity for a group of sesquiterpene lactones: inhibition of aromatase

FEBS Letters

Alvarez, Cecila I.¹  Patrito, Luis C.¹  Blanco, Javier G.¹  Genti-Raimondi, Susana¹  Flury, Alfredo¹  Gil, Roberto R.² 

[1]Departamento de Bioquı́mica Clı́nica – IMBIV (CONICET), Facultad de Ciencias Quı́micas, Universidad Nacional de Córdoba, Agencia Postal 4, CC 61, 5000 Córdoba, Argentina

[2]Departamento de Quı́mica Orgánica – IMBIV (CONICET), Facultad de Ciencias Quı́micas, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina

关键词: Aromatase inhibitor;    Sesquiterpene lactone;    Type II ligand;    Cholesterol side-chain cleavage;    Human placental microsome;    Argentine;    Asteraceae;   

DOI  :  10.1016/S0014-5793(97)00560-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A group of eleven sesquiterpene lactones isolated from different Asteraceae species from north-western Argentina were investigated for their inhibitory action on the estrogen biosynthesis. Seven of them, of different skeleton types, were found to inhibit the aromatase enzyme activity in human placental microsomes, showing IC₅₀ values ranging from 7 to 110 μM. The most active were the guaianolides 10-epi-8-deoxycumambrin B (compound 1), dehydroleucodin (compound 2) and ludartin (compound 3). These compounds were competitive inhibitors with an apparent K _i=4 μM, K _i=21 μM and K _i=23 μM, respectively. Compounds 1 and 2 acted as type II ligands to the heme iron present in the active site of aromatase cytochrome P450 (P450arom). Besides, all of them failed to affect the cholesterol side-chain cleavage enzyme activity on human placental mitochondrias. This is the first report on the aromatase inhibitory activity of this group of natural compounds.

【 授权许可】

Unknown