Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition.
The inhibitory potency of ursolic acid extracted from Ilex paraguariensis, a plant used in South American population for a tea preparation known as maté, and its derivatives to inhibit aromatase activity was assessed and compared to a phytoestrogen apigenin and a steroidal aromatase inhibitor 4-hyroxyandrostenedione (4-OHA). Among all compounds tested only ursolic acid 1 showed an efficient and dose-dependent aromatase inhibition with IC50 value of 32 microM as did apigenin (IC50=10 microM), whereas IC50 value of 4-OHA was 0.8 microM. Our results show that the incorporation of a metallocene moiety into the ursolic acid derivatives decreases the aromatase inhibition. Moreover, comparison of the structure/inhibitory potency relationship of compounds indicates that the presence of cycle A and the configuration of C3-OH and C17-COOH seems to be more favourable to recognize the active site of aromatase and to block its activity.
Gnoatto
Simone C B
SC
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre 90610-000, RS, Brazil.
Dassonville-Klimpt
Alexandra
A
Da Nascimento
Sophie
S
Galéra
Philippe
P
Boumediene
Karim
K
Gosmann
Grace
G
Sonnet
Pascal
P
Moslemi
Safa
S
D000107:Acetylation; D000577:Amides / Q000737:chemistry; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000031:analogs & derivatives / Q000302:isolation & purification* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004951:Esterification; D006801:Humans; D030019:Ilex paraguariensis / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D010084:Oxidation-Reduction; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000097245:Ursolic Acid
D000577:Amides; D001141:Aromatase; D047072:Aromatase Inhibitors; D014315:Triterpenes; D000097245:Ursolic Acid