CN115969852A - Application of methoxyl urolithin A amide derivative - Google Patents
Application of methoxyl urolithin A amide derivative Download PDFInfo
- Publication number
- CN115969852A CN115969852A CN202211270934.8A CN202211270934A CN115969852A CN 115969852 A CN115969852 A CN 115969852A CN 202211270934 A CN202211270934 A CN 202211270934A CN 115969852 A CN115969852 A CN 115969852A
- Authority
- CN
- China
- Prior art keywords
- methoxy
- urolithin
- acetamide
- methoxyurolithin
- benzo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Abstract
The invention discloses application of methoxy urolithin A amide derivatives. The test result of the aging delaying test for caenorhabditis elegans adopted by the invention shows that 75 mu M of methoxy urolithin A and 2- ((8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxygen) -N- (pyrazine-2-ylmethyl) acetamide, N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] benzopyran-3-yl) oxy) acetamide have the effects of prolonging the life and preventing neurodegenerative diseases for caenorhabditis elegans. The invention describes new pharmacological mechanisms of the methoxy urolithin A and the two amide derivatives thereof, and provides new ideas and means for the anti-aging and neurodegenerative disease prevention of the methoxy urolithin A and the two amide derivatives thereof.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to application of methoxyurolithin A and amide derivatives thereof in preparation of medicines for preventing body aging.
Background
Aging refers to a process in which various tissues, organs, etc. of an organism undergo a series of degenerative changes with age. The characteristics of mitophagy dysfunction, genome instability, telomerase shortening, protein homeostasis imbalance, cell aging and the like are in essential connection with aging. Since the incidence of most neurodegenerative diseases also increases with the age, compared with the existing drugs, the drugs for effectively treating neurodegenerative diseases are only in the stage of relieving symptoms and have large toxic and side effects, so that the development of the drugs for treating and preventing neurodegenerative diseases is particularly urgent.
At present, models for screening anti-aging comprise a subacute rat aging model caused by D-galactose, an aging model caused by beta amyloid, a model mouse for rapid aging, a natural aging mouse model, a fish aging model, a fruit fly aging model and the like, which are widely applied to anti-aging experiments. While the nematodes are model organisms, and have the advantages that other experimental organisms do not have in the aspect of aging: caenorhabditis elegans (C.elegans) is used as a model organism, the Caenorhabditis elegans only needs 3 days for developing from eggs to adults under the condition of rich nutrition at 20 ℃, the gene of the Caenorhabditis elegans and the related gene of human have 60-80% of high conservation, and the experimental result plays an important role in prompting the effect of preventing and resisting aging of the human; the growth cycle is short, a large amount of sample nematodes can be used for experiments in a short period, and the experimental result is credible; in the research of neurodegenerative diseases, the nematode is used to easily obtain an ideal disease defect system model, has transparent body, is easy to observe and detect phenotypic characteristics, has complete nervous, motor and reproductive systems, and ensures that the nematode forms rich motor behaviors such as advancing, retreating, population tropism and the like due to the mutual coordination action among cells, so that the nematode is very easy to operate genetically and pharmacologically in the research of disease-related models, and has important significance for preventing and exploring pathogenesis and treatment methods of neurodegenerative diseases.
Ellagitannin is a polyphenol compound with a complex structure existing in plants at present, ellagic acid is metabolized by intestinal flora of human body to become urolithin, and the urolithin has biological activities of resisting oxidation, inflammation and cancer, regulating intestinal flora, resisting aging and the like.
Urolithins are metabolites of ellagitannins, which are the process by which ellagic acid loses a lactone ring and gradually removes hydroxyl groups in its chemical structure. The methoxy urolithin A is a compound obtained by separation, purification and drying, and the patent number CN 113387916 discloses a preparation method of methoxy urolithin amide derivatives. According to data, no report about the application of the methoxy urolithin A and the amide derivative thereof in the aspect of anti-aging is found at present, and the application of the methoxy urolithin A and the amide derivative thereof as anti-aging components has great practical significance.
The nomenclature and chemical structures of the methoxy urolithin A and the amide derivatives are as follows:
8UA：
methoxyurolithin A
1：
N-cyclohexyl-2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide 2:
n- (2-hydroxybenzyl) -2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide
3：
N- (cyclobutylmethyl) -2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide
4：
/>
N-benzyl-2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide
5：
2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- ((5-methylfuran-2-yl) methyl) acetamide
6：
2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide
7：
N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide
8：
2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (2- (pyridin-2-yl) ethyl) acetamide
9：
N-hexyl-2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide
Disclosure of Invention
Under the background, the invention discloses an anti-aging effect of methoxyurolithin A and amide derivatives thereof, and aims to provide a new application of methoxyurolithin A and amide derivatives thereof in preparation of anti-aging drugs.
In order to achieve the above object, the present invention adopts the following technical solutions.
The application of the methoxy urolithin A amide derivative comprises the following two compounds,
2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide
N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide; the two compounds are used for preparing the medicine for intervening and preventing the aging of the organism.
The application of the methoxy urolithin A amide derivatives and the preparation of the drugs for intervening and preventing neurodegenerative diseases.
The application of the methoxy urolithin A amide derivative and the application of the two compounds in preparing the medicines for intervening and prolonging the life of nematodes.
The application of the methoxy urolithin A amide derivatives and the application of the two compounds in preparing the medicines for preventing and treating nematode muscle damage are provided.
Further, the nematode is caenorhabditis elegans.
Furthermore, the two compounds have obvious anti-aging effect when the concentration is 75 mu M.
The technical scheme of the invention has the following advantages:
1. under the condition of lower dosage and concentration, the methoxy urolithin A amide derivative has obvious prolonging effect on the life of the caenorhabditis elegans than methoxy urolithin A, and can delay the aging process of the caenorhabditis elegans; the method is simple to operate and has the advantage of effect.
2. The movement behavior and the stress capability of the caenorhabditis elegans indicate that the methoxy urolithin A amide derivative has an obvious life prolonging effect, so that the aging is delayed, and the method has good application value and significance for far-reaching medical application.
3. The invention provides a certain theoretical basis for the application of the methoxyurolithin A and the amide derivative thereof in the anti-aging drugs, and lays a good foundation for the development of the drugs in the future.
Drawings
FIG. 1 is a graph showing the effect of various concentrations of methoxyurolithin A on the healthy life of nematodes. Wherein, (a) is the life-expectancy curve of the methoxyurolithin A nematodes with different concentrations, and (b) is the life-expectancy of the methoxyurolithin A nematodes with different concentrations.
FIG. 2 shows the effect of 75 μ M methoxyurolithin A and amide derivatives on nematode longevity. Wherein (a) a 75 μ M methoxyurolithin A nematode survival curve (b) is 75 μ M N cyclohexyl 2 ((8 methoxy 6 oxo 6H benzo [ c ] benzopyran 3 yl) oxy) acetamide survival curve (c) is 75 μ M N (2 hydroxybenzyl) 2 ((8 methoxy 6 oxo 6H benzo [ c ] benzopyran 3 yl) oxy) acetamide survival curve (d) is 75 μ M N (cyclobutylmethyl) 2 ((8 methoxy 6 oxo 6H benzo [ c ] benzopyran 3 yl) oxy) acetamide survival curve (e) is 75 μ M N benzyl 2 ((8 methoxy 6 oxo 6H benzo [ c ] benzopyran 3 yl) oxy) acetamide survival curve (f) is 75 μ M2 ((8 methoxy 6 oxo 6H benzo [ c ] benzopyran 3 yl) oxy) N ((5 methyl furan 2 yl) methyl) acetamide survival curve (g) is 75 μ M358 zxft 356H benzo [ c ] benzopyran 3 yl) oxy) N ((5 methyl) benzofuran 2 yl) methyl) acetamide survival curve (g) 358 μ M358 zxft 2H-26 g-benzyl 2H-8H-benzyl 2 (c) acetamide survival curve (g) 26 g is 75 μ M32 zxft 3H-3-benzyl 2 oxo-6H-benzo [ c ] chromen-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 ] chromen-3-yl) oxy) acetamide nematode survival curve (k) 75 μ M methoxy urolithin A average life span (l) 75 μ M methoxy urolithin A and amide derivative nematode average life span.
FIG. 3 is a graph of the effect of 4,8, 75 μ M on 12 days, methoxyurolithin A and 6,7 amide derivatives on nematode locomotor activity. Wherein (a) 75 μ M methoxyurolithin A flexion of the body on day 4 (b) 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide flexion of the body on day 4 (c) 75 μ M methoxyurolithin A head swing (d) on day four 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide for day 4 (e) 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide swing of the body on day 75 μ M2- (8-methoxy-6H-benzo [ c ] chromen-3-yl) acetamide and N- (8 zxft 8-methoxy-3-yl) acetamide swing (e) for day 75 μ M2- (8-methoxy-3-methoxy-methyl) acetamide, 5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide body bending (g) 75 μ M methoxy urolithin A head wobble (H) on day 8 to 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide on day 8 and N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide head wobble (i) 75 μ M methoxy urolithin A body bending (j) on day twelfth 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3262 z3262-difluorobenzyl) -2- (8-methoxy-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3262 zxft) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) acetamide head wobble (l 75 μ M -oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide head wobbles.
FIG. 4 is a graph of the effect of 75 μ M methoxyurolithin A and 6,7 amide derivatives on nematode oxidative stress ability. Wherein (a) is a 75 μ M oxidative stress survival curve for methoxyurolithin A (b) is a 75 μ M oxidative stress survival curve for 2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide (c) is a 75 μ M N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide oxidative stress survival curve (d) is an average life span for 75 μ M oxidative stress for methoxyurolithin A (e) is an average life span for 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide.
FIG. 5 is a graph of the effect of 75 μ M methoxyurolithin A and 6,7 amide derivatives on nematode heavy metal capacity assessment. Wherein (a) is a 75 μ M methoxyurolithin A heavy metal survival curve (b) is a 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide heavy metal survival curve (c) is a 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide heavy metal survival curve (c) is a 75 μ M M N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide heavy metal survival curve (d) is a 75 μ M methoxyurolithin A heavy metal average lifetime (e) is a 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide average lifetime.
FIG. 6 is a graph of the effect of 75 μ M methoxyurolithin A and 6,7 amide derivatives on nematode learning and memory. Wherein (a) is 75 μ M methoxy urolithin A learning memory (b) is 75 μ M2- ((8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide and N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide learning memory.
FIG. 7 shows the effect of methoxyurolithin A and 6,7 amide derivatives on the growth state of E.coli. 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 ] chromen-3-yl) oxy) -N- (pyrazin-2-ylmethyl) acetamide on the E.coli growth curve (c) is the effect of N- (3,5-difluorobenzyl) -2- (8-methoxy-6-oxo-6H-benzo [ c ] chromen-3-yl) oxy) acetamide on the 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. For those skilled in the art to which the invention pertains, several simple deductions or substitutions can be made without departing from the spirit of the invention, and all shall be considered as belonging to the protection scope of the invention.
1. Test materials and reagents
The C.elegans strain and E.coli op50 to which they belong in the test were purchased from Caenorha bd itis Genetics Center (CGC);
c.elegans strain: wild type N2
Methoxy urolithin a and amide derivatives thereof: synthesized in Changzhou university
Paraquat was obtained from Sigma Aldrich trade company, inc., and other reagents were obtained from Shanghai Biotech company, inc
NGM culture medium: 3g Nacl,2.5g tryptone, 17g agar, 25ml phosphate buffer, 975ml distilled water, sterilization at 121 ℃ for 20min, cooling to about 50-70 ℃, membrane sterilization, addition of 5mol/L cholesterol solution 1mL,1mol/L anhydrous MgSO (MgSO) after sterilization, and addition of 1mol/L cholesterol solution 4 Solution 1mL,1mol/L CaCl 2 1ml of the suspension was added to the medium, plated on a plate, cooled to solidify, and placed in a refrigerator at 4 ℃.
100mM NaCl 5.85g, peptone 2.5g, agar 17g, distilled water 1L.
Preparing an LB culture medium:
(1) liquid culture medium: separately weighing peptone, yeast extract and NaCl 10g, 5g and 10g, adding distilled water to a constant volume of 1L,121 deg.C, sterilizing for 20min, and refrigerating at 4 deg.C for 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, fixing the volume at 121 ℃, sterilizing for 20min, pouring the mixture into a flat plate, and freezing for later use in a refrigerator at 4 ℃ after solidification.
M9 buffer solution: na (Na) 2 HPO 4 6g，KH 2 PO4 3g，NaCl5g，MgSO 4 .7H 2 O 0.25g，H 2 O1L.1mol/L phosphate buffer: k is 2 HPO 4 3.56g，KH 2 PO4 10.83g，H 2 O100ml。
1mg/mLMgSO 4 Solution: collecting MgSO4 powder 120.3g, adding distilled water, diluting to volume of 1L, sterilizing at 121 deg.C for 20 min.
1mg/mLCaCl 2 Solution: taking 110.9g of CaCl2 powder, adding distilled water, metering to 1L, sterilizing at 121 deg.C for 20 min.
5mol/L cholesterol solution: 0.25g of cholesterol was dissolved in 50mL of absolute ethanol and aseptically filtered through a membrane using a needle filter for use.
50% of glycerin: sterilizing 100% glycerol 5mL in 5mL distilled water at 121 deg.C for 20min, cooling, and storing in 4 deg.C refrigerator.
And (3) nematode freezing and storing liquid: 0.3g of NaCl, KH 2 PO4 0.055g，KH 2 PO 4 0.3g, 21.5mL of glycerol, 50mL of distilled water, 20min sterilization at 121 ℃ for standby.
2. Method of producing a composite material
Example 1 extension of the longevity of C.elegans by Methoxyuritol A and Uretinin amide derivatives
Test drugs:
negative controls were prepared 0.1% DMSO.
Positive control methoxy urolithin A and its amide derivatives were dissolved in 0.1% DMSO to prepare a stock solution.
Life test:
and (3) performing constant-temperature culture by using synchronized L4-stage nematodes at 20 ℃. DMSO in 0.1% in solvent control group, and 10-100 μ M methoxyurolithin A in positive control group. Counting can be carried out from the transfer moment, and the day is switched to be recorded as the 0 th day of the life test. The number of nematodes surviving, dead and lost was recorded daily to obtain the mean life of each group and the data was analyzed for survival.
Life test of methoxy urolithin a and its amide derivatives:
methoxy urolithin a was used as a control, and compared with the amide derivatives at the optimum concentration, the number of nematodes alive, dead and lost was recorded daily to obtain the average life of each group, and the data was analyzed for survival.
And (4) analyzing results:
the results are shown in FIG. 1, which is the effect of 10. Mu.M-100. Mu.M methoxyurolithin A on nematode longevity. Lifetime tests were carried out using 10. Mu.M, 25. Mu.M, 50. Mu.M, 75. Mu.M and 100. Mu.M as administration groups at different concentrations and 0.1% DMSO as a control group. The results show that 75 μ M methoxyurolithin A extends the mean life of wild type nematodes, shifting the survival curve to the right. Wherein the average life span of N2 nematodes at 75 μ M is 14.10% in FIG. 1, the average life span of N2 nematodes at 6,7 amide derivative is higher than that of negative controls 16.54% and 14.81% in FIG. 2, and it can be seen that 6,7 amide derivative prolongs the life span of nematodes as compared to methoxyurolithin A, which is shown in this example to prolong the life span of C.elegans, and at 75 μ M, the anti-aging effect of methoxyurolithin A is significantly improved but less than that of 6,7 amide derivative.
Example 2: methoxyuridine A and amide derivative for improving nematode motion ability
Test drugs: negative controls were prepared 0.1% DMSO.
The positive control, methoxyurolithin A and its amide derivatives, were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
measuring the exercise capacity:
intervention with nematode dosing synchronized to L4 phase on day four, day eight and day twelfth. 10 nematodes were placed on the blank NGM medium using M9 buffer, and after 1min recovery, the number of head swings within 1min and the number of body bends within 20s were recorded.
And (4) analyzing results:
the number of body bends and head swings within 1min for nematodes at day four, day eight and day twelfth of the dosing intervention are shown in figure 3. The body bending times and the head swinging times of 75 mu M methoxyurolithin A on the fourth day, the eighth day and the twelfth day nematodes are better improved than those of a control group, and meanwhile, the 6,7 amide derivative has obvious improvement effect compared with the methoxyurolithin A as shown in figure 3. This example demonstrates that 6,7 amide derivatives increase nematode motility over methoxyurolithin a, resulting in improved health, and lateral responses to their anti-aging effects.
Example 3: methoxyurolithin A and amide derivatives improve stress ability of nematodes
Test drugs: negative controls were prepared 0.1% DMSO.
Positive control methoxy urolithin A and its amide derivatives were dissolved in 0.1% DMSO to prepare a stock solution.
The experimental method comprises the following steps:
(1) Oxidizing stress of paraquat: after 48h of administration of the synchronized post-culture medium to L4 nematodes, they were transferred to liquid medium containing paraquat at a concentration of 160mM and the number of nematode deaths and survivals were recorded every 1 h.
And (4) analyzing results:
the nematode oxidative stress results for 48h of dosing intervention are shown in figure 4. The results show that the average life span of the nematode oxidative stress of the 75 mu M methoxyurolithin A administration group is increased by 11.68 percent compared with the control group. 5363 compared with methoxy urolithin A, the amide derivative of 6,7 is respectively 49.06% and 17.43% higher than the negative control, meanwhile, 6,7 amide derivative can be seen in the figure to improve the survival time of the nematode stress capability, and the result of the example shows that 6,7 amide derivative improves the stress capability of the nematode and has the anti-aging effect compared with methoxy urolithin A.
Example 4: methoxyurolithin A and amide derivatives improve heavy metal resistance of nematodes
Test drugs: negative controls were prepared 0.1% DMSO.
The positive control, methoxyurolithin A and its amide derivatives, were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
synchronized L4 phase nematode dosing was used for 48h,48h followed by a final concentration of 180 μ M copper chloride solution, after which the number of viable nematodes was recorded once a day until all nematodes died.
The experimental results are as follows:
the anti-heavy metals of the nematodes after 48h administration are shown in FIG. 5. The results show that the average life of 75 μ M methoxyurolithin A is improved by 6.75% compared with the control group, and the average life of 6,7 amide derivatives is respectively 19.07% and 13.64% higher than that of the negative control group. The results of this example demonstrate that 6,7 amide derivatives have better heavy metal resistance than methoxyurolithin a.
Example 5: the methoxy urolithin A and amide derivatives improve the learning ability of nematodes
Test drugs: negative controls were prepared 0.1% DMSO.
The positive control, methoxyurolithin A and its amide derivatives, were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
chemotrending capacity assay
Synchronized L4-phase nematodes are respectively exposed to an experimental group and a control group for 72h, a 100mM NaCl culture medium is prepared for high-temperature and high-pressure sterilization, and the nematodes M9 are washed for 2-3 times until the nematodes are subjected to starvation culture in a new culture medium for 4h. Blank media and media containing 100mM NaCl were separately drilled out overnight for 14h with a cork drill in test plates, which were transferred to test plates as shown in FIG. 8: blank NGM and 100mM NaCl blank NGM were drilled at 0.5cm from both ends of the plate with a cork drill as sample and control marks, respectively, so that the two marks were aligned with the center point. Two straight lines are drawn at the positions 2cm away from the center of the circle. 0.5mol/L NaN was added before the test 3 The nematode is transferred to the starting point, and the trend index (chemotaxis index) = (N) is determined after 1h A -N C )/N；N A Number of nematodes in NaCl group, N C Number of nematodes in control group, N = total number of nematodes.
And (4) analyzing results:
the learning ability of the methoxy urolithin A and 6,7 amide derivatives is shown in FIG. 6. It can be seen that the learning ability of the control group is 0.023, and the learning ability of the 75 μ M methoxyurolithin A is 0.1,6,7 amide derivatives is 0.28,0.17. The results show that the learning ability of the adult nematodes on the fourth day can be remarkably improved by 75 mu M methoxyurolithin A and 6,7 amide derivatives thereof.
Example 6: effect of 75 μ M urolithinamide derivatives on growth status of Escherichia coli
Test drugs: the negative control was prepared in 0.1% DMSO.
The positive control, methoxyurolithin A and its amide derivatives, were dissolved in 0.1% DMSO to prepare stock solutions.
The experimental method comprises the following steps:
preparing an LB liquid culture medium after autoclaving, and processing the following steps: 1. blank group 2, add op50, add methoxy urolithin A and its 6,7 amide derivatives 4, add op50 and methoxy urolithin A and its 6,7 amide derivatives. And (3) taking a blank group as a control, firstly measuring the group added with oxyurolithin A and 6,7 amide derivatives thereof, then placing the other two groups into a shaking table at 37 ℃, measuring the absorbance of the oxyurolithin A and the 6,7 amide derivatives thereof at OD595 every 30min within 390min, and recording and drawing an escherichia coli OD value growth curve.
And (4) analyzing results:
FIG. 7 is the effect of 75 μ M methoxyurolithin A and its 6,7 amide derivatives on the growth state of E.coli. As shown in FIG. 7, the OP50 growth curve in LB liquid medium to which 75. Mu.M methoxyurolithin A and its 6,7 amide derivative were added was similar to that in LB liquid medium to which no administration group was added, and the results of this example demonstrate that the life prolonging effect of 75. Mu.M methoxyurolithin A and its 6,7 amide derivative is independent of its antimicrobial effect and food availability.
Claims (6)
1. The application of the methoxyl urolithin A amide derivative is characterized in that the methoxyl urolithin A amide derivative is two compounds as follows,
the two compounds are used for preparing the medicine for intervening and preventing the aging of the organism.
2. The use of methoxy urolithin a amide derivatives according to claim 1, wherein the two compounds are used for the preparation of a medicament for the intervention of the prevention of neurodegenerative diseases.
3. The use of methoxyurolithin a carboxamide derivatives as claimed in claim 1, wherein both compounds are used for the preparation of a medicament for the intervention of prolonging nematode life.
4. The use of methoxyurolithin a amide derivatives according to claim 1, wherein both compounds are used for the manufacture of a medicament for the intervention of prevention of nematode muscle damage.
5. The use of methoxyurolithin A amide derivatives according to claim 3 or 4, wherein the nematode is C.
6. The use of methoxyurolithin a carboxamide derivatives as claimed in claim 1, wherein the anti-ageing effect is pronounced at 75 μ M of the two compounds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211270934.8A CN115969852A (en) | 2022-10-17 | 2022-10-17 | Application of methoxyl urolithin A amide derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211270934.8A CN115969852A (en) | 2022-10-17 | 2022-10-17 | Application of methoxyl urolithin A amide derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115969852A true CN115969852A (en) | 2023-04-18 |
Family
ID=85968775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211270934.8A Pending CN115969852A (en) | 2022-10-17 | 2022-10-17 | Application of methoxyl urolithin A amide derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115969852A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9872850B2 (en) * | 2010-12-23 | 2018-01-23 | Amazentis Sa | Compositions and methods for improving mitochondrial function and treating neurodegenerative diseases and cognitive disorders |
| CN113336735A (en) * | 2021-06-08 | 2021-09-03 | 常州大学 | Urolithin compound, preparation method, pharmaceutical composition and application |
| CN113387916A (en) * | 2021-07-15 | 2021-09-14 | 常州大学 | Urolithin PDE2 inhibitor compound and preparation method thereof |
-
2022
- 2022-10-17 CN CN202211270934.8A patent/CN115969852A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9872850B2 (en) * | 2010-12-23 | 2018-01-23 | Amazentis Sa | Compositions and methods for improving mitochondrial function and treating neurodegenerative diseases and cognitive disorders |
| CN113336735A (en) * | 2021-06-08 | 2021-09-03 | 常州大学 | Urolithin compound, preparation method, pharmaceutical composition and application |
| CN113387916A (en) * | 2021-07-15 | 2021-09-14 | 常州大学 | Urolithin PDE2 inhibitor compound and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| KARAR T. SHUKUR 等: "Design, synthesis, and biological evaluation of new urolithinamides as multitarget agents against Alzheimer\'s disease", 《 ARCHIV DER PHARMAZIE》, vol. 345, pages 1 - 3 * |
| WANG L, XIAOKAITI Y, 等，: "Inhibition of PDE2 reverses beta amyloid induced memory impairment through regulation of PKA/PKG-dependent neuro-inflammatory and apoptotic pathways", 《SCIENTIFIC REPORTS》，, vol. 7, pages 1 - 8 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102257130B1 (en) | Composition for Prevention or Treatment of Neurological or Mental Disorders Comprising Extracellular Vesicles Derived from Lactobacillus paracasei | |
| Persson | Mushrooms | |
| Li et al. | Synthesis and neuroprotective action of xyloketal derivatives in Parkinson’s disease models | |
| US4885308A (en) | Method and compositions for treatment of parkinsonism syndrome in mammals | |
| US20220110984A1 (en) | Application of Dubosiella Newyorkensis in Prolonging Lifespan and Anti-Aging | |
| CN114507205A (en) | Dihydromyricetin pyrrolidine compound and preparation method and application thereof | |
| CN105646611B (en) | Two caffeoyl spermidine derivatives glucosides of one kind and application thereof | |
| CN115969852A (en) | Application of methoxyl urolithin A amide derivative | |
| US11672838B2 (en) | Composition for prevention or treatment of neurological or mental disorders comprising extracellular vesicles derived from Lactobacillus paracasei | |
| JP2022048204A (en) | Method for adaptation | |
| CN109680021A (en) | A kind of low-molecular weight chondroitin sulfate and its preparation process and the application in treatment Alzheimer disease | |
| CN105816851B (en) | A kind of antidote for preventing and treating fish cyanophycean toxin nosotoxicosis | |
| CN115581689A (en) | Application of urolithin B amide derivatives | |
| CN1533776A (en) | Application of N-acetly glucosamine in the preparation of medicine for treating local injury and full body syndrome due to virus or bacterial infestation | |
| CN107812001A (en) | Pectolinarigenin is used as 6 OHDA Nervous toxicities antagonists, α synapse nucleoproteins inhibitor and preventing and treating Parkinson's purposes | |
| CN109381473A (en) | Scutelloside is in the application for preparing gestational diabetes Fetal neurotubules malformation drug | |
| Ponce-Macotela et al. | Mortality and morphological changes in Giardia duodenalis induced by exposure to ethanolic extracts of Justicia spicigera | |
| CN108403980B (en) | Hypoglycemic plant extract effective part and preparation method and application thereof | |
| CN108670961B (en) | Establishment method and application of caenorhabditis elegans drunkenness model for rapidly screening alcohol-dispelling plants | |
| CN111110671A (en) | Application of fraxins in resisting aquatic animal streptococcus agalactiae infection | |
| CN110604823A (en) | Method for rapidly screening anti-saccharification and/or anti-aging substances | |
| CN104774239B (en) | More piece spore viridin compounds and application thereof | |
| CN117224513A (en) | Application of paeonol in preparation of anti-aging and life-prolonging products | |
| CN104844544B (en) | Split-ring knobbed spore viridin type compound and application thereof | |
| CN115073374B (en) | Alpha-glucosidase inhibitor and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |