CN109265467B - A heptacyclic lactone compound derived from fructus Ligustri Lucidi, and its application as medicine for treating senile dementia - Google Patents
A heptacyclic lactone compound derived from fructus Ligustri Lucidi, and its application as medicine for treating senile dementia Download PDFInfo
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- CN109265467B CN109265467B CN201811317265.9A CN201811317265A CN109265467B CN 109265467 B CN109265467 B CN 109265467B CN 201811317265 A CN201811317265 A CN 201811317265A CN 109265467 B CN109265467 B CN 109265467B
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- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The invention relates to a heptacyclic lactone compound derived from traditional Chinese medicine glossy privet fruit and application thereof as an anti-senile dementia medicine, wherein the heptacyclic lactone compound has a structure shown in a formula I:
Description
Technical Field
The invention belongs to the field of traditional Chinese medicine extracts, and particularly relates to a heptacyclic lactone compound derived from traditional Chinese medicine glossy privet fruit and application thereof as an anti-senile dementia medicine.
Background
Fructus Ligustri Lucidi is dry mature fruit of Ligustrum lucidum ait of Oleaceae, and is mainly produced in Zhejiang and Jiangsu, and its main chemical components include triterpenes, iridoid glycosides, flavonoids, phenethyl alcohol, amino acids, polysaccharides, volatile oil, and anthocyanins. Recent researches show that the glossy privet fruit extract has certain antioxidant activity in vitro. The invention provides a heptacyclic lactone compound derived from glossy privet fruit, and the compound has certain acetylcholinesterase inhibition activity and antioxidant activity.
Disclosure of Invention
The invention provides a heptacyclic lactone compound derived from traditional Chinese medicine glossy privet fruit or pharmaceutically acceptable salt thereof, which is characterized in that the heptacyclic lactone compound has a structure shown in a formula I:
another embodiment of the present invention provides a process for the preparation of a compound of formula I as described above, characterized by the steps of:
(1) pulverizing dried fructus Ligustri Lucidi to 20-80 mesh, soaking in ethyl acetate at room temperature for 36-48 hr, filtering, and concentrating the filtrate to obtain extract;
(2) dispersing the extract obtained in the step (1) with water, extracting with diethyl ether for 2-3 times, combining organic layers, concentrating, and performing normal phase silica gel column chromatography to obtain the compound of formula I.
In the step (1), the dosage of the ethyl acetate is 3-5 times of the mass of the dried glossy privet fruit; the amount of water in the step (2) is 8-10 times of the mass of the extract, the volume of ether used in each extraction is the same as that of water, 200-300-mesh silica gel is used in normal phase silica gel column chromatography, and the eluent is a petroleum ether/ethyl acetate mixed solvent with the volume ratio of 3:1 or a dichloromethane/methanol mixed solvent with the volume ratio of 30: 1.
In another embodiment of the invention there is provided the use of a compound of formula I as described above, or a pharmaceutically acceptable salt thereof, in the preparation of an acetylcholinesterase inhibitor.
Another embodiment of the present invention provides the use of a compound of formula I as described above or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of alzheimer's disease.
Another embodiment of the present invention provides the use of a compound of formula I as described above, or a pharmaceutically acceptable salt thereof, as an antioxidant.
Another embodiment of the present invention provides the use of a compound of formula I, or a pharmaceutically acceptable salt thereof, as described above for scavenging free radicals. The radical is preferably DPPH radical or superoxide anion radical.
Another embodiment of the present invention provides a pharmaceutical composition characterized in that the pharmaceutical composition comprises the above compound of formula I or a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutical composition can also comprise a proper amount of pharmaceutically acceptable pharmaceutic adjuvants.
Detailed Description
In order to facilitate a further understanding of the invention, the following examples are provided to illustrate it in more detail. However, these examples are only for better understanding of the present invention and are not intended to limit the scope or the principle of the present invention, and the embodiments of the present invention are not limited to the following.
Example 1
(1) Pulverizing dried fructus Ligustri Lucidi (1.0kg) to 20-80 mesh, soaking in ethyl acetate (3.0kg) at room temperature for 48 hr, filtering, and concentrating the filtrate to obtain extract (9.62 g);
(2) dispersing the extract (2.0g) obtained in the step (1) with water (16mL), extracting with diethyl ether for 3 times (16mL multiplied by 3), combining organic layers, concentrating, and performing normal phase silica gel column chromatography (200-mesh silica gel with 300 meshes, and petroleum ether/ethyl acetate 3/1) to obtain the compound (46mg, yellow solid) of the formula I.
A 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).
example 2
(1) Pulverizing dried fructus Ligustri Lucidi (1.0kg) to 20-80 mesh, soaking in ethyl acetate (5.0kg) at room temperature for 36 hr, filtering, and concentrating the filtrate to obtain extract (10.72 g);
(2) taking the extract (2.0g) obtained in the step (1), dispersing the extract with water (20mL), extracting the extract with diethyl ether for 2 times (20mL multiplied by 2), combining organic layers, concentrating the organic layers, and performing normal phase silica gel column chromatography (200-mesh silica gel with 300 meshes, and dichloromethane/methanol-30/1) to obtain the compound (43mg, yellow solid, and the structure confirmation data is consistent with the report) of the formula I.
Example 3 acetylcholinesterase inhibitory Activity (AchE)
1mg of the compound of the formula I was dissolved in DMSO to prepare a solution having a mass concentration of 10. mu.g/mL, and acetylcholinesterase inhibitory activity (AchE) was tested by reference to the 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), and as a result, the AchE inhibitory rate of the compound of the formula I was 54.3% at a concentration of 10. mu.g/mL.
Example 4 Oxidation resistance test
The DPPH radical scavenging ability and superoxide anion scavenging ability of the compound of formula I were tested by the methods described in "Wanghitong, et al," analysis of ingredients of yellow tea soup and research on antioxidant activity ", Anhui college of agriculture, proceedings of 2018,45 (5)", and the results showed that the compounds of formula I exhibited DPPH radical and superoxide anion scavenging rates of 56.3% and 47.2%, respectively, at a concentration of 10. mu.g/mL.
Claims (4)
1. A preparation method of a heptacyclic lactone compound from traditional Chinese medicine glossy privet fruit is characterized by comprising the following steps:
(1) pulverizing dried fructus Ligustri Lucidi to 20-80 mesh, soaking in ethyl acetate at room temperature for 36-48 hr, filtering, and concentrating the filtrate to obtain extract;
(2) dispersing the extract obtained in the step (1) with water, extracting with diethyl ether for 2-3 times, combining organic layers, concentrating, and performing normal phase silica gel column chromatography to obtain heptacyclic lactone compound;
in the step (1), the dosage of the ethyl acetate is 3-5 times of the mass of the dried glossy privet fruit; the amount of water in the step (2) is 8-10 times of the mass of the extract, the volume of ether used in each extraction is the same as that of water, 200-mesh and 300-mesh silica gel is used in normal phase silica gel column chromatography, and the eluent is a petroleum ether/ethyl acetate mixed solvent with the volume ratio of 3:1 or a dichloromethane/methanol mixed solvent with the volume ratio of 30: 1;
the heptacyclic lactone compound has a structure shown in formula I:
2. use of the heptacyclic lactone compound prepared according to claim 1 in the preparation of an acetylcholinesterase inhibitor.
3. Use of the heptacyclic lactone compound prepared according to claim 1 for the preparation of an anti-senile dementia medicament.
4. Use of the heptacyclic lactone compound prepared according to claim 1 in the preparation of an antioxidant.
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