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

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 mu 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 K-i = 4 mu M, K-i = 21 mu M and K-i = 23 mu M, respectively, Compounds 1 and 2 acted as type II ligands to the heme iron present in the ache 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. (C) 1997 Federation of European Biochemical Societies.