CN-118978504-B - Isopentenyl flavone compound, and preparation method and application thereof

Abstract

The invention relates to isopentenyl flavonoid compounds, a preparation method and application thereof, belongs to the technical field of medicines, and in particular relates to three isopentenyl flavonoid compounds broussoflavonol C, daphnegiranol G and daphnegiranol E separated from daphne (DAPHNE GIRALDII NITSCHE) of daphne of daphnaceae by chromatographic methods such as silica gel column chromatography, macroporous resin, ODS column chromatography and HPLC. The invention also tests the inhibitory activity of the three compounds on Hep3B cells. It was finally found that the above-mentioned compounds exert antitumor activity by inhibiting the growth activity of tumor cells. The preparation method is simple, the reproducibility is good, the purity of the obtained compound is high, and part of the compound has obvious anti-tumor activity.

Inventors

• SONG SHAOJIANG
• HUANG XIAOXIAO
• XIN BENSONG
• ZHAO BOYUAN
• YAO GUODONG
• BAI MING
• DONG SHUHUI
• LV TIANMING

Assignees

• 沈阳药科大学

Dates

Publication Date

20260512

Application Date

20240802

Claims (8)

1. 1. An isopentenyl flavonoid compound is characterized by being a compound shown as follows; 。
2. 2. a process for the preparation of an isopentenyl flavonoid as set forth in claim 1, comprising the steps of: (1) Extracting dried daphne root bark and stem bark with ethanol, mixing the extractive solutions, concentrating to obtain extract, extracting the obtained extract with ethyl acetate, extracting with n-butanol, subjecting the ethyl acetate part to silica gel column chromatography, gradient eluting with dichloromethane-methanol, and collecting 4 fractions Fr. A-Fr. D; (2) Subjecting fraction Fr. A to HP-20 column chromatography, subjecting to ODS column chromatography, eluting with ethanol-water gradient, and collecting total 7 fractions Fr. A1-Fr. A7; (3) The eluted fraction Fr. A5 was subjected to semi-preparative HPLC and further purified by acetonitrile-water system to give the isopentenyl flavonoids.
3. 3. The method for preparing isopentenyl flavonoids according to claim 2, wherein in the step (1), the gradient of dichloromethane-methanol is 100:1-1:1, and the ethanol is industrial ethanol with the concentration of 70% and is subjected to reflux extraction for 3 times each for 2 hours.
4. 4. The method for preparing isopentenyl flavonoids according to claim 2, wherein in the step (2), the gradient of ethanol-water is 20% -90%.
5. 5. The method for producing prenylflavonoids according to claim 2, wherein in the step (3), the acetonitrile-water ratio of the compound 3 is 27:78, v/v.
6. 6. A pharmaceutical composition comprising the isopentenyl flavonoid of claim 1 and a pharmaceutically acceptable carrier or excipient.
7. 7. The use of the isopentenyl flavonoid compound of claim 1 in preparing anti-liver cancer drugs.
8. 8. The use of the pharmaceutical composition of claim 6 in the preparation of anti-liver cancer drugs.

Description

Isopentenyl flavone compound, and preparation method and application thereof Technical Field The invention belongs to the technical field of medicines, and particularly relates to 3 novel isopentenyl flavonoid compounds separated from daphne root bark and stem bark, a preparation method thereof and application thereof in anti-tumor aspect. Background Daphne (DAPHNE GIRALDII NITSCHE) is a plant of the genus daphne (Daphne) of the family daphnaceae (THYMELAEACEAE). The root bark and the stem bark are used as medicines, and the root bark and the stem bark of daphne tanguticum (Daphne tangutica) and concave She Ruixiang (Daphne retusa) are used as medicines together to prepare girald daphne bark. Mainly distributed in provinces of Shaanxi, gansu, qinghai, sichuan, xinjiang and the like. Warm nature, pungent and bitter taste, small toxicity, and has the effects of dispelling wind, removing dampness, relieving pain, removing blood stasis, etc. Modern pharmacological research shows that daphne giraldii has various pharmacological activities such as anti-inflammatory, analgesic, anti-tumor, immunoregulation, antioxidation, bacteriostasis, neuroprotection and the like. The daphne root bark and stem bark have rich chemical components including coumarin, flavonoid, diterpenoid, etc., and the isopentenyl flavonoid has high antitumor activity. The isopentenyl flavone (PRENYLATED FLAVONOIDS) is mainly distributed in leguminous and Moraceae plants, and is separated from daphne giraldii in daphnaceae plants. It is characterized in that one or more isopentenyl side chains are connected on the mother nucleus of the flavonoid through C-C or C-O bonds, so that the lipophilicity of the flavonoid compound is obviously increased to improve the bioactivity and bioavailability of the flavonoid compound. Due to the higher ortho-position activity of the hydroxyl on the benzene ring, the isoamylene base is substituted at the C-6, C-8 and C-3', C-5' positions of the A ring and the B ring. In the natural plant synthesizing process, the hexatomic pyran ring type or pentatomic furan ring type isopentenyl flavone is formed by cyclization, oxidization, dehydration and other reactions with the ortho-position phenolic hydroxyl. Disclosure of Invention The invention aims to provide a series of isopentenyl flavonoid compounds separated from daphne root bark and stem bark, a preparation method thereof and application thereof in antitumor drugs. The structure of the isopentenyl flavonoid compound is as follows: The preparation method of the isopentenyl flavonoid compound comprises the following steps: Extracting dry root bark and stem bark of Daphne Giraldii Nitsche with ethanol, concentrating the extractive solution under reduced pressure, mixing the extractive solutions, concentrating to obtain extract, sequentially extracting with ethyl acetate and n-butanol, subjecting the ethyl acetate extract to silica gel column chromatography, HP-20 macroporous resin, ODS, HPLC, etc., and finally separating to obtain the above 3 new compounds. The specific operation is as follows: (1) Extracting dried daphne root bark and stem bark with ethanol, mixing the extractive solutions, concentrating to obtain extract, extracting the extract with ethyl acetate and n-butanol, subjecting the ethyl acetate part to silica gel column chromatography, and collecting 4 fractions Fr.A-Fr.D; (2) Subjecting the fraction Fr.A to HP-20 and ODS column chromatography, eluting with ethanol-water gradient, and collecting 7 fractions Fr.A1-Fr.A7; (3) The fraction fr.a5 obtained after elution is subjected to semi-preparative HPLC and further purified by an acetonitrile-water system to obtain the isopentenyl flavonoid. As an alternative, wherein: In the step (1), the gradient of dichloromethane-methanol is 100:1-1:1, and the ethanol is industrial ethanol with the concentration of 70 percent, and the reflux extraction is carried out for 3 times each for 2 hours. In the step (2), the gradient of ethanol-water is 20% -90%. In step (3), three compounds were used with acetonitrile-water ratios of broussoflavonol C (38:62, v/v), daphnegiranol G (25:75, v/v), daphnegiranol E (27:78, v/v), respectively. The structural analysis of the novel isopentenyl flavonoid compounds (broussoflavonol C, daphnegiranol G, daphnegiranol E) prepared by the invention is shown below. Compound 1, yellow amorphous powder (methanol). Hresis gives an excimer ion peak [ m+h ] +m/z 437.1972(calcd for C26H29O6, 437.1959), and the molecular formula of the compound can be determined to be C 26H29O6 by combining 1H-NMR,13 C-NMR spectrum, the unsaturation degree is calculated to be 13, and the 1H-NMR,13 C-NMR signal is attributed, meanwhile, the plane structure is determined by HMBC spectrum, and finally the compound is determined to be an isopentenyl flavonoid structure. And the compound is found to be a novel compound which is not reported through SCIFINDER search, and is named broussoflavonol C. Its 1 H NMR spectrum,