CN109265467A

CN109265467A - A kind of seven macrolide compounds in Fruits of Ligustrum Lucidum Ait source and its application as anti senile dementia drug

Info

Publication number: CN109265467A
Application number: CN201811317265.9A
Authority: CN
Inventors: 徐玥
Original assignee: 扬州工业职业技术学院
Current assignee: Li Chengze; Li Yanjie; Ordos Tianjiao Resource Development Co ltd
Priority date: 2018-11-07
Filing date: 2018-11-07
Publication date: 2019-01-25
Anticipated expiration: 2038-11-07
Also published as: CN109265467B

Abstract

The present invention relates to a kind of seven macrolide compounds in Fruits of Ligustrum Lucidum Ait source and its as the application of anti senile dementia drug, seven macrolide compounds have structure shown in Formulas I:

Description

Seven macrolide compounds in a kind of Fruits of Ligustrum Lucidum Ait source and its as anti-senile dementia The application of drug

Technical field

The invention belongs to Chinese medical extract fields, and in particular to a kind of seven macrolide compounds in Fruits of Ligustrum Lucidum Ait source and Its application as anti senile dementia drug.

Background technique

The fruit of glossy privet is the dry mature fruit of Oleaceae plants glossy privet Ligustrum lucidum Ait., and main product is in Zhejiang The ground such as river, Jiangsu, main chemical component have triterpenes, iridoid glycosides, flavonoids, phenylethanol, amino acid, more Sugar, volatile oil, anthocyanidin etc..Research in recent years, which shows glossy privet fruit extract in vitro, has certain antioxidant activity.The present invention A kind of seven macrolide compounds in fruit of glossy privet source are provided, and the compound has certain inhibiting activity of acetylcholinesterase And antioxidant activity.

Summary of the invention

The present invention provides seven macrolide compounds or its pharmaceutically acceptable salt in a kind of Fruits of Ligustrum Lucidum Ait source, special Sign is that seven macrolide compounds have structure shown in Formulas I:

Another embodiment of the present invention provides the preparation method of above-mentioned compound of formula I, it is characterised in that including walking as follows It is rapid:

(1) dry ligustrum lucidum powder is broken to 20-80 mesh, at room temperature, is impregnated 36-48 hours with ethyl acetate, filtering, filter Liquid is concentrated to give medicinal extract；

(2) it after the medicinal extract obtained step (1) is water-dispersible, is extracted 2-3 times with ether, after merging organic layer concentration, warp Normal-phase silica gel column chromatography is to get compound of formula I.

The dosage of ethyl acetate is 3-5 times of dry glossy privet protonatomic mass in step (1)；The dosage of water is leaching in step (2) 8-10 times of cream quality, extraction is identical as the volume of water using the volume of ether every time, and normal-phase silica gel column chromatography uses 200-300 Mesh silica gel, eluant, eluent are the dichloromethane that the petrol ether/ethyl acetate mixed solvent either volume ratio that volume ratio is 3:1 is 30:1 Alkane/methanol mixed solvent.

Another embodiment of the present invention provides above-mentioned compound of formula I or its pharmaceutically acceptable salt is preparing acetyl gallbladder Application in alkali esterase inhibitor.

Another embodiment of the present invention provides above-mentioned compound of formula I or its pharmaceutically acceptable salt is preparing anti-ageing year Application in anti-dementia agent.

Another embodiment of the present invention provides above-mentioned compound of formula I or its pharmaceutically acceptable salt as antioxidant Using.

Another embodiment of the present invention provides above-mentioned compound of formula I or its pharmaceutically acceptable salt and is removing free radical The application of aspect.The preferred DPPH free radical of the free radical, ultra-oxygen anion free radical.

Another embodiment of the present invention provides a kind of pharmaceutical composition, it is characterised in that the pharmaceutical composition is with above-mentioned formula Compound I or its pharmaceutically acceptable salt are as effective component.The pharmaceutical composition, which may also include, suitable can pharmaceutically connect The pharmaceutic adjuvant received.

Specific embodiment

For the ease of a further understanding of the present invention, examples provided below has done more detailed description to it.But It is that these embodiments are only not supposed to be a limitation to the present invention or implementation principle for better understanding invention, reality of the invention The mode of applying is not limited to the following contents.

Embodiment 1

(1) the dry fruit of glossy privet (1.0kg) is crushed to 20-80 mesh, at room temperature, impregnates 48 with ethyl acetate (3.0kg) Hour, filtering, filtrate are concentrated to give medicinal extract (9.62g)；

(2) after the medicinal extract (2.0g) for taking step (1) to obtain is dispersed with water (16mL), 3 times (16mL × 3) are extracted with ether, After merging organic layer concentration, through normal-phase silica gel column chromatography (200-300 mesh silica gel, petrol ether/ethyl acetate=3/1) to get Formulas I Compound (46mg, yellow solid).

Compound of formula I:¹H NMR(500MHz,acetone-d₆)δ:11.98(1H,s,19-OH),6.89(1H,s,H- 18), 6.76 (1H, s, H-4), 5.70 (1H, d, J=14.5Hz, H-11a), 5.58 (1H, d, J=14.5Hz, H-11b), 4.98 (1H, d, J=11.5Hz, H-22a), 4.73 (1H, d, J=11.5Hz, H-22b), 3.44 (1H, d, J=16.0Hz, H-14a), 3.08 (1H, d, J=16.0Hz, H-14b), 2.78 (2H, s, CH₃-25),2.58(2H,s,CH₃-26)；¹³C NMR(125MHz, acetone-d₆)δ:193.9(C,C-15),170.7(C,C-21),170.5(C,C-1),164.7(C,C-19),164.3(C, C-3),156.4(C,C-7),150.8(C,C-17),150.0(C,C-9),147.2(C,C-5),145.2(C,C-24),133.2 (C,C-12),122.2(C,C-16),120.8(CH,C-18),118.2(CH,C-4),114.8(C,C-8),112.3(C,C- 10),110.1(C,C-6),103.3(C,C-20),97.7(C,C-2),74.4(CH₂,C-22),67.6(CH₂,C-11),49.9 (C,C-23),49.6(CH₂,C-14),23.6(CH₃,C-25),23.4(CH₃,C-26)；ESI-MS m/z 491.1[M+H]⁺； [α]_D ²⁰+248(c 0.46,CH₃OH).

Embodiment 2

(1) the dry fruit of glossy privet (1.0kg) is crushed to 20-80 mesh, at room temperature, impregnates 36 with ethyl acetate (5.0kg) Hour, filtering, filtrate are concentrated to give medicinal extract (10.72g)；

(2) after the medicinal extract (2.0g) for taking step (1) to obtain is dispersed with water (20mL), 2 times (20mL × 2) are extracted with ether, After merging organic layer concentration, through normal-phase silica gel column chromatography (200-300 mesh silica gel, methylene chloride/methanol=30/1) to get Formulas I Compound (43mg, yellow solid, structural identification data and report are consistent).

3 inhibiting activity of acetylcholinesterase of embodiment (AchE)

1mg compound of formula I is taken, is dissolved with DMSO, the solution that mass concentration is 10 μ g/mL is configured to, referring to Ellman method (Ellman G L, Courtney K D, et al.A new and rapid colorimetric determination of Acetylcholinesterase activity [J] .Biochemical Pharmacology, 1961,7 (2): 88-95) it surveys It tries inhibiting activity of acetylcholinesterase (AchE), the results showed that, under the concentration of 10 μ g/mL, the AchE inhibiting rate of compound of formula I Up to 54.3%.

The anti-oxidant experiment of embodiment 4

Reference literature " Wang Haisong, etc., " yellow big tea millet paste constituent analysis and antioxidant activity research ", " Agricultural University Of Anhui Journal ", 2018,45 (5) " in the method recorded, DPPH free radical scavenging ability, the superoxide anion for testing compound of formula I be clear Removing solid capacity, the results showed that, under the concentration of 10 μ g/mL, clearance rate point of the compound of formula I to DPPH free radical, superoxide anion It Wei 56.3%, 47.2%.

Claims

1. seven macrolide compounds or its pharmaceutically acceptable salt in a kind of Fruits of Ligustrum Lucidum Ait source, it is characterised in that described seven Macrolide compounds have structure shown in Formulas I:

2. the preparation method of compound of formula I described in claim 1, it is characterised in that include the following steps:

(1) dry ligustrum lucidum powder is broken to 20-80 mesh, at room temperature, is impregnated 36-48 hours with ethyl acetate, filtering, filtrate are dense Contract to obtain medicinal extract；

(2) it after the medicinal extract obtained step (1) is water-dispersible, is extracted 2-3 times with ether, after merging organic layer concentration, through positive Silica gel column chromatography is to get compound of formula I.

3. preparation method as claimed in claim 2, it is characterised in that the dosage of ethyl acetate is dry fruit of glossy privet matter in step (1) 3-5 times of amount；The dosage of water is 8-10 times of medicinal extract quality in step (2), and extraction uses the volume of ether and the body of water every time Product is identical, and normal-phase silica gel column chromatography uses 200-300 mesh silica gel, and eluant, eluent is that the petrol ether/ethyl acetate that volume ratio is 3:1 is mixed The methylene chloride/methanol mixed solvent that bonding solvent either volume ratio is 30:1.

4. compound of formula I described in claim 1 or its pharmaceutically acceptable salt are in preparation acetylcholinesterase inhibitor Application.

5. compound of formula I described in claim 1 or its pharmaceutically acceptable salt are preparing answering in anti senile dementia drug With.

6. the application of compound of formula I described in claim 1 or its pharmaceutically acceptable salt as antioxidant.

7. the application of compound of formula I described in claim 1 or its pharmaceutically acceptable salt in terms of removing free radical.

8. application as claimed in claim 7, it is characterised in that the preferred DPPH free radical of the free radical, superoxide anion are free Base.

9. a kind of pharmaceutical composition, it is characterised in that the pharmaceutical composition is with compound of formula I described in claim 1 or its pharmacy Upper acceptable salt is as effective component.

10. pharmaceutical composition as claimed in claim 9, it is characterised in that the pharmaceutical composition, which may also include, suitable pharmaceutically may be used The pharmaceutic adjuvant of receiving.