CN115969852B - Application of methoxy urolithin A amide derivative - Google Patents
Application of methoxy urolithin A amide derivative Download PDFInfo
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- CN115969852B CN115969852B CN202211270934.8A CN202211270934A CN115969852B CN 115969852 B CN115969852 B CN 115969852B CN 202211270934 A CN202211270934 A CN 202211270934A CN 115969852 B CN115969852 B CN 115969852B
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- acetamide
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- -1 methoxy urolithin A amide Chemical class 0.000 title claims abstract description 92
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of methoxy urolithin A amide derivatives. The results of the anti-caenorhabditis elegans senescence test adopted by the invention show that 75 mu M of methoxyurolithin A and 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide have the functions of prolonging the service life and preventing neurodegenerative diseases for caenorhabditis elegans. The invention discloses a novel pharmacological mechanism of methoxy urolithin A and two amide derivatives, and provides a novel thought and means for the application of methoxy urolithin A and two amide derivatives thereof in resisting aging and preventing neurodegenerative diseases.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of methoxyurinary calculus A and an amide derivative thereof in preparation of a medicine for preventing body aging.
Background
Aging refers to the process by which various tissues, organs, etc., of an organism undergo a series of degenerative changes with age. Mitochondrial autophagy dysfunction, genomic instability, shortening of telomerase, imbalance in protein homeostasis, cellular senescence and other characteristics are all in essential association with senescence. As the incidence rate of most neurodegenerative diseases is increased along with the increase of the age, compared with the existing medicines, the effective medicines for treating the neurodegenerative diseases are only in the stage of relieving symptoms and have larger toxic and side effects, so that the development of medicines capable of treating and preventing the neurodegenerative diseases is particularly urgent.
At present, a subacute rat aging model, a beta amyloid aging model, a rapid aging model mouse, a natural aging mouse model, a fish aging model, a drosophila aging model and the like which are aiming at screening anti-aging models caused by D-galactose are widely applied to anti-aging experiments. Nematodes, as model organisms, have the advantage that none of the other experimental organisms possess in terms of aging: caenorhabditis elegans (Caenorhabditis elegans, c.elegans) as a model organism, only 3 days are needed for the development of adults from eggs under the condition of rich nutrition at 20 ℃, the genes of the caenorhabditis elegans and related genes of human beings have high conservation of 60% -80%, and experimental results play an important role in prompting the anti-aging effect of human beings; the growth period is short, a large amount of nematodes with sample size can be used for experiments in a short period, and the experimental results are reliable; the nematode is used in the research of neurodegenerative diseases, an ideal disease defect type system model is easy to obtain, the body is transparent, the observation and detection of phenotypic characteristics are easy, the model has complete nerves, movement and reproductive systems, and the interaction among cells enables the nematode to form rich movement behaviors such as advancing, retreating, group chemotaxis and the like, so that the nematode can be easily operated in genetics and pharmacology in the model research of related diseases, and the model has important significance for preventing and exploring pathogenesis and treatment methods of neurodegenerative diseases.
Ellagitannins are a type of polyphenol compounds with complex structures existing in plants at present, and ellagic acid is metabolized into urolithin through intestinal flora of human bodies, and the urolithin has biological activities of resisting oxidation, resisting inflammation, resisting cancer, regulating intestinal flora, resisting aging and the like.
Urolithin is a metabolite of ellagitannin, and in chemical structure, urolithin is a process in which ellagic acid loses a lactone ring and gradually removes hydroxyl groups. Methoxy urolithin A is a compound obtained by separation, purification and drying, and patent number CN 113387916 discloses a preparation method of methoxy urolithin amide derivatives. By referring to the data, no report on the application of the methoxy urolithin A and the amide derivatives thereof in the anti-aging aspect is found at present, and the application of the methoxy urolithin A and the amide derivatives thereof as anti-aging components has great practical significance.
The name and chemical structure of methoxy urolithin A and amide derivatives are as follows:
8UA：
Methoxy urolithin A
1：
N-cyclohexyl-2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide
2：
N- (2-hydroxybenzyl) -2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide
3：
N- (cyclobutylmethyl) -2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide
4：
N-benzyl-2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide
5：
2- ((8-Methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- ((5-methylfuran-2-yl) methyl) acetamide
6：
2- ((8-Methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide
7：
N- (3, 5-difluorobenzyl) -2- ((8-methoxy-6-oxo-6-H-benzo [ c ] benzopyran-3-yl) oxy) acetamide
8：
2- ((8-Methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyridin-3-ylmethyl) acetamide
9：
N-hexyl-2- ((8-methoxy-6-oxo-6-H-benzo [ c ] benzopyran-3-yl) oxy) acetamide
Disclosure of Invention
Under the background, the invention discloses an anti-aging effect of methoxy urolithin A and amide derivatives thereof, and aims to provide a new application of the methoxy urolithin A and the amide derivatives thereof in preparation of anti-aging medicines.
In order to achieve the above object, the present invention adopts the following technical scheme.
The application of methoxy urolithin A amide derivatives is that the methoxy urolithin A amide derivatives are two compounds,
The two compounds are used for preparing medicines for intervening in preventing body aging.
The application of methoxy urolithin A amide derivatives is that the two compounds are used for preparing medicines for intervening and preventing neurodegenerative diseases.
The application of methoxyurinary calculus A amide derivatives is that the two compounds are used for preparing medicines for interfering and prolonging the service life of nematodes.
The application of methoxy urolithin A amide derivatives is that the two compounds are used for preparing medicines for intervening in preventing injury of muscles of line worms.
Further, the nematode is caenorhabditis elegans.
Further, the two compounds have obvious anti-aging effect at 75 mu M.
The technical scheme of the invention has the following advantages:
1. Under the condition of lower dosage and concentration, the methoxyurinary calculus A amide derivative has obvious effect of prolonging the service life of caenorhabditis elegans compared with methoxyurinary calculus A, and can delay the aging process of caenorhabditis elegans; the method is simple to operate and has the advantage of effect.
2. The exercise behavior and the stress capability of the caenorhabditis elegans show that the methoxyurinary calculus A amide derivative has obvious effect of prolonging the service life, further delays aging, and has good application value and significance for far-reaching medical application.
3. The invention provides a certain theoretical basis for the application of methoxy urolithin A and amide derivatives thereof in anti-aging medicaments, and lays a good foundation for the development of medicaments in the future.
Drawings
Figure 1 shows the effect of different concentrations of methoxyurinary calculus a on the health life of insects. Wherein, (a) is the survival curve of the methoxy urolithin A nematodes with different concentrations, and (b) is the average life span of the methoxy urolithin A nematodes with different concentrations.
FIG. 2 shows the effect of 75. Mu.M methoxy urolithin A and amide derivatives on the longevity of insects. Wherein (a) a methoxyurolithin A nematode survival curve (b) of 75. Mu.M is 75. Mu. M N-cyclohexyl-2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide nematode survival curve (c) is 75. Mu. M N- (2-hydroxybenzyl) -2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide nematode survival curve (d) is 75. Mu. M N- (cyclobutylmethyl) -2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide nematode survival curve (e) is 75. Mu. M N-benzyl-2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide nematode survival curve (f) is 75. Mu.M 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide nematode survival curve (d) 75. Mu.m 2- ((8-methoxy-6-oxo-6H-benzopyran-3-yl) oxy) acetamide nematode survival curve (e) 75. Mu.m 2- ((8-methoxy-methyl) -2- ((8-methoxy-6-benzopyran-3-yl) oxy) acetamide nematode survival curve (e) is 75. Mu. 6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide nematode survival curve (H) 75 μ M N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide nematode survival curve (i) 75 μM 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (2- (pyridin-2-yl) ethyl) acetamide nematode survival curve (j) 75 μ M N-hexyl-2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide nematode survival curve (k) 75 μM methoxy urolithin A average life (l) 75 μM methoxy urolithin A and amide derivative nematode average life.
FIG. 3 shows the effect of 75. Mu.M methoxyurolithin A and 6,7 amide derivatives on nematode locomotor activity on days 4,8, 12. Wherein (a) is 75. Mu.M methoxy urolithin A body curvature on day 4 (b) is 75. Mu.M 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzopyran-3-yl) oxy) acetamide body curvature on day 4 (c) is 75. Mu.M methoxy urolithin A head swing on day four (d) is 75. Mu.M 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide head swing (e) at day 8 75. Mu.M methoxyurolithin A body swing (f) at day 8 75. Mu.M 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzopyran-3-yl) oxy) acetamide body swing (g) at day 8 75. Mu.M methoxyurolithin A head swing (H) at day 8 75. Mu.M 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide head swing (i) 75. Mu.M methoxy urolithin A body swing (j) 75. Mu.M 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide body swing (k) 75. Mu.M methoxy urolithin A head swing (l) 75. Mu.M 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-oxo-6H-benzopyran-3-yl) oxy) acetamide head swing (i) 75. Mu.M twelfth day.
FIG. 4 is a graph showing the effect of 75. Mu.M methoxy urolithin A and 6,7 amide derivatives on nematode oxidative stress ability. Wherein (a) is 75 μM methoxy urolithin A oxidative stress survival (b) is 75 μM 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide oxidative stress survival (c) is 75 μ M N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide oxidative stress survival (d) is 75 μM methoxy urolithin A oxidative stress average lifetime (e) is 75 μM 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide oxidative stress average lifetime.
FIG. 5 is a graph showing the effect of 75. Mu.M methoxy urolithin A and 6,7 amide derivatives on nematode heavy metal capacity assessment. Wherein (a) is 75 μM of methoxyurolithin A heavy metal survival curve (b) is 75 μM of 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide heavy metal survival curve (c) 75 μ M N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide heavy metal survival curve (d) is 75 μM of methoxyurolithin A heavy metal average lifetime (e) is 75 μM of 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide heavy metal average lifetime.
FIG. 6 is a graph showing the effect of 75. Mu.M methoxy urolithin A and 6,7 amide derivatives on learning and memory of nematodes. Wherein (a) is 75 μM methoxy urolithin A learning memory (b) is 75 μM 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide learning memory.
FIG. 7 shows the effect of methoxy urolithin A and 6,7 amide derivatives on E.coli growth status. Wherein (a) is the effect of methoxyurolithin A on E.coli growth (b) is the effect of 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide on E.coli growth curve (c) is the effect of N- (3, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide on E.coli growth curve.
FIG. 8 is a graph showing the learning ability of methoxyurolithin A and 6,7 amide derivatives.
Detailed Description
The present invention will be described in further detail with reference to examples. It will be apparent to those skilled in the art that several simple deductions or substitutions may be made without departing from the spirit of the invention, and these should be considered to be within the scope of the invention.
1. Experimental materials and reagents
Both the C.elegans strain to which the test belongs and the E.coli op50 strain are purchased from Caenorha bd ITIS GENETICS CENTER (CGC);
Caenorhabditis elegans strain: wild type N2
Methoxy urolithin a and its amide derivatives: synthesized at Changzhou university
Paraquat was purchased from Sigma Aldrich trade Co., ltd, and other reagents were purchased from Shanghai Biotechnology Co., ltd
NGM medium: 3g of NaCl,2.5g of tryptone, 17g of agar, 25ml of phosphate buffer, 975ml of distilled water, sterilization at 121 ℃ for 20min, cooling to about 50-70 ℃, sterilizing by passing through a membrane, adding 1ml of 5mol/L cholesterol solution, 1ml of 1mol/L anhydrous MgSO 4 solution and 1ml of 1mol/L CaCl 2 ml into a culture medium, adding the culture medium into a flat plate, cooling and solidifying, and pouring the culture medium into a refrigerator at 4 ℃.
100MMNaCl:NaCl 5.85g, peptone 2.5g, agar 17g, distilled water 1L.
Preparing an LB culture medium:
① Liquid medium: respectively weighing peptone, yeast extract and 10g, 5g and 10g of NaCl, adding distilled water to a constant volume of 1L,121 ℃, sterilizing for 20min, and refrigerating at 4 ℃ for later use.
② Solid medium: respectively weighing 10g, 5g, 10g and 17g of peptone, yeast extract, naCl and agar powder, adding distilled water to a constant volume of 1L,121 ℃, sterilizing for 20min, pouring into a flat plate, and standing in a refrigerator at 4 ℃ after solidification.
M9 buffer ：Na2HPO4 6g,KH2PO4 3g,NaCl5g,MgSO4.7H2O 0.25g,H2O1L.
1Mol/L phosphate buffer: k 2HPO4 3.56g,KH2PO4 10.83g,H2 O100ml.
1Mg/mLMgSO 4 solution: 120.3g of MgSO4 powder is taken, distilled water is added, the volume is fixed to 1L, the temperature is 121 ℃, and the sterilization is carried out for 20min for standby.
1Mg/mLCaCl 2 solution: 110.9g of CaCl2 powder is taken, distilled water is added, the volume is fixed to 1L, the temperature is 121 ℃, and the sterilization is carried out for 20min for standby.
5Mol/L cholesterol solution: 0.25g of cholesterol was dissolved in 50mL of absolute ethanol and sterile filtered using a needle filter.
50% Glycerol: sterilizing 100% glycerol 5mL in 5mL distilled water at 121deg.C for 20min, cooling, and placing in a refrigerator at 4deg.C for use.
Nematode frozen stock solution: 0.3g of NaCl, 0.3g of KH 2PO4 0.055g,KH2PO4, 21.5mL of glycerol, 50mL of distilled water and sterilization at 121 ℃ for 20 min.
2. Method of
EXAMPLE 1 methoxy urolithin A and urolithin amide derivatives to extend the longevity of caenorhabditis elegans
Test drug:
Negative controls were formulated with 0.1% dmso.
Positive control methoxy urolithin A and its amide derivatives were dissolved in 0.1% DMSO to prepare stock solutions.
Life test:
The synchronized L4-phase nematodes were incubated at 20 ℃. The solvent control group was 0.1% DMSO and the positive control group was 10-100. Mu.M methoxy urolithin A. Counts were taken from the time of transfer, and the day of the life test was counted. The number of nematode survival, death and loss was recorded daily, the average life span of each group was obtained, and the data was subjected to survival analysis.
Life test of methoxyurolithin a and its amide derivatives:
methoxy urolithin A is used as a control, compared with the amide derivatives thereof under the optimal concentration, the survival, death and loss number of nematodes are recorded daily, the average life span of each group is obtained, and the survival analysis of the data is carried out.
Analysis of results:
The results are shown in FIG. 1 as the effect of 10. Mu.M-100. Mu.M methoxyurolithin A on the longevity of insects. Life tests were performed with 10 μm, 25 μm, 50 μm, 75 μm, 100 μm as dosing groups at different concentrations, while with 0.1% dmso as control group. The results showed that 75 μm methoxy urolithin a prolonged the average life span of wild type nematodes, allowing the survival curve to shift to the right. Wherein the average life span of the N2 nematode of 75 mu M is 14.10% as shown in figure 1, the 6,7 amide derivative in figure 2 is 16.54% and 14.81% higher than that of the methoxy urolithin A, and the 6,7 amide derivative in figure is longer than that of the methoxy urolithin A, the example shows that the methoxy urolithin A can prolong the life span of the caenorhabditis elegans, and the anti-aging effect of the methoxy urolithin A obviously improves the life span of the nematode at the dosage of 75 mu M, but the improvement degree is lower than that of the 6,7 amide derivative.
Example 2: methoxy urolithin A and amide derivatives improve nematode locomotion
Test drug: negative controls were formulated with 0.1% dmso.
Positive control methoxy urolithin A and its amide derivatives were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
Motion capability measurement:
Nematode dosing with synchronized cultures to stage L4 was used to intervene on days four, eight and twelfth. 10 nematodes were placed on a blank NGM medium with M9 buffer, and after 1min recovery, the number of head swings in 1min and the number of body bends in 20s were recorded.
Analysis of results:
The number of body curves and head swings in 1min for nematodes 20s on the fourth, eighth and twelfth days of the dosing intervention are shown in fig. 3. The body bending times and head swinging times of the nematodes on the fourth day, the eighth day and the twelfth day of 75 mu M of methoxy urolithin A are better improved than those of the control group, and meanwhile, the 6,7 amide derivatives have obvious improvement effects compared with the methoxy urolithin A as shown in figure 3. This example demonstrates that 6,7 amide derivatives have an anti-aging effect on the side of improving the exercise capacity of nematodes compared to methoxyurolithin A, resulting in improved health.
Example 3: methoxy urolithin A and amide derivatives improve the stress capability of nematodes
Test drug: negative controls were formulated with 0.1% dmso.
Positive control methoxy urolithin A and its amide derivatives were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
(1) Paraquat oxidative stress: after 48h of administration of the synchronized medium to the nematodes in stage L4, they were transferred to liquid medium of 160mM paraquat concentration, and the number of deaths and survival of the nematodes were recorded every 1 h.
Analysis of results:
The results of 48h of nematode oxidative stress after dosing intervention are shown in figure 4. The result shows that the average life of the nematode oxidative stress of the 75 mu M methoxy urolithin A administration group is improved by 11.68% compared with that of a control group. Compared with methoxy urolithin A, the 6,7 amide derivatives are 49.06 percent and 17.43 percent higher than the negative control, and meanwhile, the 6,7 amide derivatives can be seen from the figure to improve the survival time of nematode stress capability, and the results of the example show that the 6,7 amide derivatives improve the nematode stress capability compared with the methoxy urolithin A and have anti-aging effect.
Example 4: methoxy urolithin A and amide derivatives for improving nematode heavy-metal resistance
Test drug: negative controls were formulated with 0.1% dmso.
Positive control methoxy urolithin A and its amide derivatives were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
the nematode was dosed for 48h,48h with synchronized L4 phase, and a final concentration of 180 μm in copper chloride solution was added, after which the number of nematodes surviving was recorded once a day until all the nematodes died.
Experimental results:
The heavy-duty resistance of the nematodes after 48h of administration is shown in figure 5. The results showed that the average lifetime of 75 μm of methoxyurolithin a was increased by 6.75% compared to the control group and that the 6,7 amide derivatives were higher than the negative control 19.07%,13.64%, respectively. The results of this example demonstrate that 6,7 amide derivatives have better heavy metal resistance than methoxyurolithin a.
Example 5: methoxy urolithin A and amide derivatives improve learning ability of nematodes
Test drug: negative controls were formulated with 0.1% dmso.
Positive control methoxy urolithin A and its amide derivatives were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
Chemical trend ability measurement
The synchronized L4-phase nematodes are respectively exposed to an experimental group and a control group for 72 hours, 100mM NaCl culture medium is prepared for high-temperature and high-pressure sterilization, and the nematodes M9 are washed for 2-3 times to be starved and cultured in a new culture medium for 4 hours. Blank medium and culture with 100mM NaCl were drilled separately with a cork driller and allowed to stand overnight in a test plate to form a chemotactic plate into which nematodes to be tested were transferred, as shown in FIG. 8: and drilling blank NGM and 100mM NaCl blank NGM at the position 0.5cm away from the two ends of the flat plate by using a cork driller to respectively make sample marks and comparison marks, so that the two-point marks and the center point form a straight line. Drawing two straight lines at the positions 2cm away from the center of the circle. 0.5mol/L NaN 3 was added before the test to turn the nematodes to a starting point, and after 1h the trend index (chemotaxis index) = (N A-NC)/N;NA =nacl group number of nematodes, N C =control group number of nematodes, n=total number of nematodes) was determined.
Analysis of results:
The learning ability of methoxyurolithin A and 6,7 amide derivatives is shown in FIG. 6. It can be seen that the control group had a learning ability of 0.023, 75. Mu.M methoxy urolithin A, 0.1,6,7 amide derivatives, 0.28,0.17. The result shows that 75 mu M methoxy urolithin A and its 6,7 amide derivatives can raise the learning capacity of adult nematode obviously.
Example 6: influence of 75 mu M urolithin amide derivatives on growth state of Escherichia coli
Test drug: negative controls were formulated with 0.1% dmso.
Positive control methoxy urolithin A and its amide derivatives were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
LB liquid medium after autoclaving was prepared as follows: 1. blank 2, addition of op50 3, addition of methoxy urolithin a and its 6, 7 amide derivatives 4, addition of op50 and methoxy urolithin a and its 6, 7 amide derivatives. Taking blank group as control, firstly measuring and adding oxyurolithin A and 6, 7 amide derivatives thereof, then placing the other two groups into a shaking table at 37 ℃ for 390min, measuring absorbance at OD595 of the other two groups every 30min, and recording and drawing an E.coli OD value growth curve.
Analysis of results:
FIG. 7 is a graph showing the effect of 75. Mu.M methoxy urolithin A and its 6,7 amide derivatives on E.coli growth status. As shown in FIG. 7, the OP50 growth curve in LB liquid medium supplemented with 75. Mu.M of methoxyurolithin A and its 6,7 amide derivatives was similar to the OP50 growth curve in LB liquid medium not supplemented with the administration group, and the results of this example demonstrate that the life-prolonging effect of 75. Mu.M of methoxyurolithin A and its 6,7 amide derivatives was independent of its antimicrobial effect and food availability.
Claims (3)
1. The application of methoxy urolithin A amide derivatives as the only active component in preparing the anti-caenorhabditis elegans senescence medicament is characterized in that the methoxy urolithin A amide derivatives are one of the following two compounds,
The two compounds are used for preparing medicines for intervening in preventing body aging; the concentration of the two compounds was 75. Mu.M/L.
2. The use according to claim 1, wherein the two compounds are used for the preparation of a medicament for intervention in prolonging nematode life.
3. The use according to claim 1, wherein the two compounds are used for the preparation of a medicament for the intervention against muscle damage of a line insect.
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