Isolation and characterization of aromatase inhibitors from Brassaiopsis glomerulata (Araliaceae)

Abstract

The hexane-and ethyl acetate-soluble extracts of the leaves of Brassaiopsis glomerulata (Blume) Regel (Araliaceae), collected in Indonesia, were found to inhibit aromatase, the rate-limiting enzyme in the production of estrogens from androgens, in both enzyme-and cell-based aromatase inhibition (AI) assays. Bioassay-guided fractionation led to the isolation of six known compounds of the steroid and triterpenoid classes (1-6) from the hexane extract, of which 6β-hydroxystimasta-4-en-3-one (5), was moderately active in the cell-based AI assay. Fractionation of the ethyl acetate extract afforded seven pure isolates (7-13) of the modified peptide, fatty acid, monoterpenoid, and benzenoid types, including six known compounds and the new natural product, N-benzoyl-L-phenylalanine methyl ester (9). The absolute stereochemistry of 9 and the other two peptides, 7 and 8, was determined by Marfey's analysis. Linoleic acid (10) was found to be active in the enzyme-based AI assay, while 9 and (−)-dehydrololiolide (12) showed activity in the cell-based AI assay.

Natural Products as Aromatase Inhibitors

“…from various wineries, with the most active being Cabernet Sauvignon from Tanglewood (France) [86, 106, 107]. The hexane partition of the leaves of Brassaiopsis glomerulata (Blume) Regel (Araliaceae) was found to be active in microsomes [108]. The methanol and chloroform extracts of Garcinia mangostana L. (Clusiaceae) (mangosteen) were also strongly inhibitory against aromatase in microsomes [109].…”

“…sp.) in MCF-7aro cells [85], a water reflux extract of white button mushrooms [ Agaricus bisporus (J. Lange) Imbach] in MCF-7aro cells [115], red clover flowers ( Trifolium pratense L.) in a MCF-7 cell dual assay for aromatase inhibition and estrogenicity [116], mangosteen ( Garcinia mangostana L.) in SK-BR-3 cells [109], and Brassaiopsis glomerulata (Blume) Regel in SK-BR-3 cells [108]. The red clover flowers were found to inhibit aromatase at low concentrations and were also estrogenic at high concentrations.…”

“…No cellular testing was done on these compounds. N -Benzoyl- L -phenylalanine methyl ester ( 177 ), isolated from Brassaiopsis glomerulata L., was found to be weakly active in SK-BR-3 cells [108]. …”

“…Ten steroids isolated from Aglaia ponapensis Kaneh. [158], Albizia falcataria (L.) Fosberg, and Brassaiopsis glomerulata (Blume) Regel [108] were found to be inactive in microsomal aromatase testing.…”

Phytosterols as precursors for the synthesis of aromatase inhibitors: Hemisynthesis of testololactone and testolactone

“…Aromatase which is also 59 known as estrogen synthase, has always been found to be the most 60 promising target for the treatment of breast cancer [7] Atractylodes macrocephala are reported to inhibit more than 50% 78 of aromatase activity at about 10 mM concentration [9]. 6b-hy-79 droxystigmast-4-en-3-one (9) has been found to be a weak aro-80 matase inhibitor in cell-based assays [10]. Since the naturally TESLAC is regarded as a pioneer drug to treat breast cancer [11].…”