A novel activity for a group of sesquiterpene lactones: Inhibition of aromatase.

BLANCO JAVIER; GIL ROBERTO; ALVAREZ CECILIA; PATRITO LUIS; GENTI DE RAIMONDI SUSANA; FLURY A

ELSEVIER SCIENCE BV

Año: 1997 vol. 409 p. 396 - 396

bstract A group of eleven sesquiterpene lac tones isolated from different As t e rac eae species from north-western Argentina were investigated for their inhibitory action on the estrogen biosynthesis. Seven of them, of different skeleton type s, were found to inhibit the aromatase enzyme activity in human placental mi c rosome s, showing I C5 0 values ranging from 7 to 110 u M. 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 Ki= 4 [iM, Ki= 21 uM and Ki= 23 pJYl, respectively. Compounds 1 and 2 acted as type II ligands to the heme iron present in the active site of aromatase cytochrome P450 ( P 4 5 0 a r om). Besides, all of them failed to affect the cholesterol side-chain cleavage enzyme activity on human placental mi tochondrias. This is the first report on the aromatase inhibitory activity of this grou