title: A novel activity for a group of sesquiterpene lactones: inhibition of aromatase.
abstract: 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 microM. 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 microM, Ki = 21 microM and Ki = 23 microM, 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.
authors.affiliation: Departamento de Bioquímica Clínica-IMBIV (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina. jblanco@fcq.uncor.edu
authors.forename: J G
authors.initials: JG
authors.lastname: Blanco
authors.forename: R R
authors.initials: RR
authors.lastname: Gil
authors.forename: C I
authors.initials: CI
authors.lastname: Alvarez
authors.forename: L C
authors.initials: LC
authors.lastname: Patrito
authors.forename: S
authors.initials: S
authors.lastname: Genti-Raimondi
authors.forename: A
authors.initials: A
authors.lastname: Flury
mesh_terms: D000897:Anti-Ulcer Agents / Q000494:pharmacology; D047072:Aromatase Inhibitors; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000897:Anti-Ulcer Agents; D047072:Aromatase Inhibitors; D007783:Lactones; D011257:Pregnancy Proteins; D012717:Sesquiterpenes; C079949:dehydroleucodine; D002786:Cholesterol Side-Chain Cleavage Enzyme