6,8-Diprenylorobol

Life Sci. 2002 Aug 9;71(12):1449-63.

Anti-Helicobacter pylori flavonoids from licorice extract.[Pubmed: 12127165]

Licorice is the most used crude drug in Kampo medicines (traditional Chinese medicines modified in Japan). The extract of the medicinal plant is also used as the basis of anti-ulcer medicines for treatment of peptic ulcer.
METHODS AND RESULTS:
Among the chemical constituents of the plant, glabridin and glabrene (components of Glycyrrhiza glabra), licochalcone A (G. inflata), licoricidin and licoisoflavone B (G. uralensis) exhibited inhibitory activity against the growth of Helicobacter pylori in vitro. These flavonoids also showed anti-H. pylori activity against a clarithromycin (CLAR) and amoxicillin (AMOX)-resistant strain. We also investigated the methanol extract of G. uralensis. From the extract, three new isoflavonoids (3-arylcoumarin, pterocarpan, and isoflavan) with a pyran ring, gancaonols A[bond]C, were isolated together with 15 known flavonoids. Among these compounds, vestitol, licoricone, 1-methoxyphaseollidin and gancaonol C exhibited anti-H. pylori activity against the CLAR and AMOX-resistant strain as well as four CLAR (AMOX)-sensitive strains. Glycyrin, formononetin, isolicoflavonol, glyasperin D, 6,8-Diprenylorobol, gancaonin I, dihydrolicoisoflavone A, and gancaonol B possessed weaker anti-H. pylori activity.
CONCLUSIONS:
These compounds may be useful chemopreventive agents for peptic ulcer or gastric cancer in H. pylori-infected individuals.

J. Funct. Foods, 2017, 29:104-14.

Orobol derivatives and extracts from Cudrania tricuspidata fruits protect against 6-hydroxydomamine-induced neuronal cell death by enhancing proteasome activity and the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1[Reference: WebLink]

We investigated the neuroprotective effects of orobol derivatives and ethanol extracts from Cudrania tricuspidata fruits.
METHODS AND RESULTS:
Among the nine isolates from a 50% ethanol extract from Cudrania tricuspidata fruits (CTE50), orobol (OB), 6-prenylorobol (POB), and 6,8-Diprenylorobol (DPOB) showed neuroprotective effects in 6-OHDA-induced SH-SY5Y cell death. In addition, CTE50 and the three orobol derivatives (OB, POB, and DPOB) attenuated the cleavage of caspase-3, caspase-9, and PARP and inhibited the excessive generation of ROS. Furthermore, it enhanced the 6-OHDA-induced dysfunction of proteasome activity and reduced the accumulation of ubiquitin conjugated-proteins and the polyubiquitination of α-synuclein and synphilin-1. The proteasome inhibitor MG132 blocked the neuroprotective effects and the enhanced proteasome activity produced by CTE50 and the three orobol derivatives.
CONCLUSIONS:
These results demonstrate that CTE50 and three orobol derivatives protect against 6-OHDA-induced neurotoxicity by enhancing the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1, suggesting that they might be possible candidates for the treatment of neurodegenerative diseases.

J Asian Nat Prod Res. 2017 May;19(5):510-518.

Prenylated isoflavones from Cudrania tricuspidata inhibit NO production in RAW 264.7 macrophages and suppress HL-60 cells proliferation.[Pubmed: 27649772]

METHODS AND RESULTS:
Inhibitory effects of NO production in RAW 264.7 macrophages guided the isolation of nine prenylated isoflavones, including a new cudraisoflavone L (1) and eight known metabolites furowanin B (2), erysubin A (3), wighteone (4), lupalbigenin (5), laburnetin (6), isolupalbigenin (7), 6,8-Diprenylorobol (8), millewanin H (9) from the leaves of Cudrania tricuspidata.
CONCLUSIONS:
At the concentration of 10 μM, compounds 1, 2, and 4 significantly inhibited NO production with the inhibitory values of 72.5 ± 2.4, 66.9 ± 1.8, and 55.4 ± 2.7%, respectively. In addition, all of isolated compounds 1-9 showed promising cytotoxic effects toward HL-60 cells (IC50 4.3 ± 0.7 to 18.0 ± 1.7 μM).

Nat. Prod. Sci., 2011(17):206-11.

Isolation of Prenylated Isoflavonoids from Cudrania tricuspidata Fruits that Inhibit A2E Photooxidation.[Reference: WebLink]

METHODS AND RESULTS:
High-performance liquid chromatography coupled to an online -based assay (online HPLC-) system was used to determine the principal antioxidants in Cudrania tricuspidata fruits. Six prenylated isoflavonoids (1 - 6) were isolated from C. tricuspidata fruits according to the online HPLC- system. The structures of isolated compounds, alpiniumisoflavone (1), 6,8-Diprenylorobol (2), 6,8-diprenylgenistein (3), pomiferin (4), 4'-methylalpiniumisoflavone (5), and osajin (6) were identified by their retention time, UV spectra, ESI-MS, and NMR data.
CONCLUSIONS:
Among these compounds, 6,8-Diprenylorobol (2) and pomiferin (4) reduced A2E photooxidation in a dose dependent manner.

Planta Med. 2001 Feb;67(1):87-9.

Antifungal chalcones from Maclura tinctoria.[Pubmed: 11270732]

Five prenylated flavonoids, including one new natural product, were isolated from an ethanol extract of the leaves of Maclura tinctoria (L.) Gaud.
METHODS AND RESULTS:
The new compound has been characterized as 2',4',4,2''-tetrahydroxy-3'-[3''-methylbut-3''-enyl]chalcone (1). The known compounds were identified as 2',4',4-trihydroxy-3'-[3''-methylbut-3''-enyl]chalcone (isobavachalcone) (2), 4,2'-dihydroxy-2''-[1-hydroxy-1-methylethyl]-2'',3''-dihydrofurano[4'',5'':3',4']chalcone (bakuchalcone) (3), 4,4',5''-trihydroxy-6'',6''-dimethyldihydropyrano[2'',3'':5',6'']chalcone (bavachromanol) (4), and 5,7,3',4'-tetrahydroxy-6,8-diprenylisoflavone (6,8-Diprenylorobol) (5). All the isolated compounds were evaluated against the AIDS-related opportunistic fungal pathogens, Candida albicans and Cryptococcus neoformans.
CONCLUSIONS:
Compound 2 was active against both yeasts.

J. Health Sci., 2006, 52(2):186-91.

Anti-Estrogenic Activity of Prenylated Isoflavones from Millettia pachycarpa: Implications for Pharmacophores and Unique Mechanisms[Reference: WebLink]

Phytoestrogens containing isoflavonoids are thought to exhibit preventative effects on estrogen-responsive diseases. Chemical modifications, such as prenylation, in biosynthetic processes enhance the structural variety of isoflavonoids and prompted us to carry out a structure-activity relationship study.
METHODS AND RESULTS:
We determined the estrogenic/anti-estrogenic activities and estrogen receptor (ER)-binding affinities of eight kinds of prenylated isoflavones isolated from Millettia pachycarpa (Leguminosae), and those of two kinds of non-prenylated compounds (genistein and daidzein). By comparing these compounds, the pharmacophores for estrogenic/anti-estrogenic activities were elucidated. None of the tested compounds (except genistein) were estrogenic on ligand-dependent yeast-two hybrid assay. On the other hand, 5 isoflavones showed distinct anti-estrogenic activity. Unexpectedly, the most potent antagonists, isoerysenegalensein E and 6,8-Diprenylorobol, showed anti-estrogenic activity comparable to that of 4-hydroxytamoxifen, a typical ER antagonist.
CONCLUSIONS:
This suggests that genistein became an antagonist after prenylation and hydroxylation. The pharmacophores providing genistein with strong anti-estrogenic activity were as follows: prenyl groups of the 6- and 8-positions on the A-ring, hydroxyl group of the 6-prenyl moiety or the B-ring (catechol form), non-cyclization of the prenyl group with the A-ring, and non-hydroxylation of the 8-prenyl group on the A-ring. The ER-binding affinities of the isoflavonoids were not sufficiently high to explain their potent antagonistic activities, thus suggesting 17β-estradiol-non-competitive mechanisms.