| Kinase Assay: |
| Bioorg Med Chem Lett. 2019 Mar 15;29(6):839-843. | | Osthenol, a prenylated coumarin, as a monoamine oxidase A inhibitor with high selectivity.[Pubmed: 30686752] |
METHODS AND RESULTS:
Osthenol (6), a prenylated coumarin isolated from the dried roots of Angelica pubescens, potently and selectively inhibited recombinant human monoamine oxidase-A (hMAO-A) with an IC50 value of 0.74 µM and showed a high selectivity index (SI > 81.1) for hMAO-A versus hMAO-B. Compound 6 was a reversible competitive hMAO-A inhibitor (Ki = 0.26 µM) with a potency greater than toloxatone (IC50 = 0.93 µM), a marketed drug. Isopsoralen (3) and bakuchicin (1), furanocoumarin derivatives isolated from Psoralea corylifolia L., showed slightly higher IC50 values (0.88 and 1.78 µM, respectively) for hMAO-A than 6, but had low SI values (3.1 for both). Other coumarins tested did not effectively inhibit hMAO-A or hMAO-B. A structural comparison suggested that the 8-(3,3-dimethylallyl) group of 6 increased its inhibitory activity against hMAO-A compared with the 6-methoxy group of scopoletin (4). Molecular docking simulations revealed that the binding affinity of 6 for hMAO-A (-8.5 kcal/mol) was greater than that for hMAO-B (-5.6 kcal/mol) and that of 4 for hMAO-A (-7.3 kcal/mol). Docking simulations also implied that 6 interacted with hMAO-A at Phe208 and with hMAO-B at Ile199 by carbon hydrogen bondings.
CONCLUSIONS:
Our findings suggest that Osthenol, derived from natural products, is a selective and potent reversible inhibitor of MAO-A, and can be regarded a potential lead compound for the design of novel reversible MAO-A inhibitors. | | Planta Med. 2002 Feb;68(2):162-3. | | Inhibitors of 5alpha -reductase type I in LNCaP cells from the roots of Angelica koreana.[Pubmed: 11859469] |
METHODS AND RESULTS:
A prenylated coumarin, Osthenol (1) and a sesquiterpene, bisabolangelone (2) have been isolated as active principles with 5alpha-reductase type I inhibitory effects in LNCaP cells from the roots of Angelica koreana Max. by bioassay-guided chromatographic fractionation.
METHODS AND RESULTS:
Osthenol exhibited a highly potent inhibitory activity on 5alpha-reductase type I in LNCaP cells with an IC50 value of 0.1 microg/ml, which is about 200 times more potent than the positive control, finasteride (IC50 = 19.8 microg/ml).
Bisabolangelone also inhibited the activity of 5alpha-reductase type I in LNCaP cells (IC50 = 11.6 microg/ml), indicating that these compounds are possible candidates for the development of new drugs to treat human endocrine disorders associated with overproduction of DHT by 5 alpha-reductase type I. In addition, four compounds isooxypeucedanin, oxypeucedanin hydrate, oxypeucedanin and isoimperatorin were also isolated and found to be inactive in the 5alpha-reductase assay systems used in the present study. | | Planta Med. 1998 Aug;64(6):525-9. | | Inhibitory effects of Angelica pubescens f. biserrata on 5-lipoxygenase and cyclooxygenase.[Pubmed: 9741298 ] |
METHODS AND RESULTS:
Linoleic acid, osthol, Osthenol and two polyacetylenes, falcarindiol and 11(S),16(R)-dihydroxyoctadeca-9Z,17-diene-12,14-diyn-1 -yl acetate were found to be the most active compounds responsible for the inhibitory activity of the dichloromethane extract of the roots of Angelica pubescens f. biserrata on 5-lipoxygenase (5-LO) and cyclooxygenase (COX-1) in vitro.
CONCLUSIONS:
They showed prominent inhibitory effect on 5-LO with IC50 values of 27.9 microM, 36.2 microM, 43.1 microM, 9.4 microM and 24.0 microM, respectively. Linoleic acid, Osthenol, falcarindiol and 11(S), 16(R)-dihydroxyoctadeca-9Z,17-diene-12,14-diyn-1-yl acetate exhibited inhibitory activity on COX-1 with IC50 values of 13.3 microM, 64.3 microM, 66.0 microM and 73.3 microM. |
|
| Cell Research: |
| Planta Med. 2005 Jan;71(1):84-7. | | Antitumor-promoting activity of coumarins from citrus plants.[Pubmed: 15678381] |
METHODS AND RESULTS:
In order to identify antitumor-promoting agents, we performed primary in vitro screening of 31 coumarins isolated from 11 plants of the Citrus species (Rutaceae), examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells.
Some of the 8-substituted coumarins, 8-formyl-7-hydroxycoumarin (5), Osthenol (7), demethylauraptenol (8), osthenon (9) and dihydroosthenon (10), were found to significantly inhibit EBV-EA activation (IC50: 129-207 mol ratio/32 pmol TPA).
CONCLUSIONS:
Osthenol (7) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. |
|
| Structure Identification: |
| Zhongguo Zhong Yao Za Zhi. 2017 Jun;42(11):2102-2109. | | Chemical constituents from lipophilic parts in roots of Angelica dahurica cv.Yubaizhi.[Pubmed: 28822155 ] | The chemical constituents from lipophilic parts in the roots of Angelica dahurica cv. Yubaizhi were studied in this paper.
METHODS AND RESULTS:
The compounds were separated and purified by repeated column chromatographic methods on silica gel and HPLC, and the chemical structures of compounds were determined by spectral data analyses. Thirty-three compounds were obtained and identified as isoimperatorin (1), imperatorin (2), stigmasterol (3), isooxypeucedanin (4), pabulenol (5), psoralen (6), bergapten (7), isodemethylfuropinarine (8), phellopterin (9), Osthenol (10), alloimperatorin (11), xanthotoxin (12), xanthotoxol (13), isopimpinellin (14), alloisoimperatorin (15), β-sitosterol (16), oxyalloimperatorin (17), pabularinone (18), 5-hydroxy-8-methoxypsoralen (19), columbianetin (20), heracol (21), isogosferol (22), 2″R-neobyakangelicol (23), byakangelicin ethoxide (24), byakangelicin (25), oxypeucedanin hydrate (26), uracil (27), umbelliferone (28), bergaptol (29), demethylfuropinarine (30), isobyakangelicol (31), oxypeucedanin ethanolate (32), heraclenol (33).
CONCLUSIONS:
Among them, compounds 8, 10, 17, 21, and 30 were obtained from the roots of title plant for the first time. |
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