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A novel activity for a group of sesquiterpene lactones: inhibition of aromatase
Author(s) -
Blanco Javier G.,
Gil Roberto R.,
Alvarez Cecila I.,
Patrito Luis C.,
Genti-Raimondi Susana,
Flury Alfredo
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00560-7
Subject(s) - aromatase , sesquiterpene , stereochemistry , enzyme , microsome , cytochrome p450 , chemistry , active site , ic50 , asteraceae , enzyme assay , biochemistry , enzyme inhibitor , heme , biology , in vitro , ecology , genetics , cancer , breast cancer
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 IC 50 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.