CN109232384B - Aristolochia lactam compound and preparation method and application thereof - Google Patents
Aristolochia lactam compound and preparation method and application thereof Download PDFInfo
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- -1 Aristolochia lactam compound Chemical class 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 241000726094 Aristolochia Species 0.000 title abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 42
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- 239000003208 petroleum Substances 0.000 claims description 18
- 238000000605 extraction Methods 0.000 claims description 17
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract description 13
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
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- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 4
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- KPVDACWQNCRKTG-UHFFFAOYSA-N Aristololactam II Natural products C=1C(C(=O)N2)=C3C2=CC2=CC=CC=C2C3=C2OCOC2=1 KPVDACWQNCRKTG-UHFFFAOYSA-N 0.000 description 3
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
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- UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 description 2
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- 125000000596 cyclohexenyl group Chemical class C1(=CCCCC1)* 0.000 description 2
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- BBFQZRXNYIEMAW-UHFFFAOYSA-N aristolochic acid I Chemical compound C1=C([N+]([O-])=O)C2=C(C(O)=O)C=C3OCOC3=C2C2=C1C(OC)=CC=C2 BBFQZRXNYIEMAW-UHFFFAOYSA-N 0.000 description 1
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- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
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Images
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/90—Benzo [c, d] indoles; Hydrogenated benzo [c, d] indoles
- C07D209/92—Naphthostyrils
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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Abstract
The invention discloses an aristolochia lactam compound and a preparation method and application thereof, and three new aristolochia lactam compounds are obtained by separating roots of gleditsia rostrata to obtain aristolochia lactam compounds, namely aristolochia lactam (hydroxyl is at position 7 and is called compound A) connected with 4 methoxy groups and 1 hydroxyl group, aristolochia lactam (hydroxyl is at position 4 and is called compound C) connected with 3 methoxy groups and 1 hydroxyl group, and the compound A and the compound C are isomers. Wherein the compound B and the compound C have obvious antibacterial activity on the bacillus cereus.
Description
Technical Field
The invention belongs to the technical field of biochemical medicines, and particularly relates to an aristolochia lactam compound as well as a preparation method and application thereof.
Background
The Annonaceae (Annonaceae) saponaria (Dasymaschalon) plants are distributed in tropical regions of Asia in total of 16 kinds, and have good curative effect on diseases such as malaria and rheumatic osteodynia as folk common medicinal plants. In recent decades, scholars at home and abroad screen the biological activity of the crude extract or the monomer compound of the saponaria plant, and find that the saponaria plant has wide pharmacological activity, such as antibacterial, anti-inflammatory, antiviral, antitumor, antimalarial and the like. In the research of chemical components, compounds such as alkaloid, flavone, cyclohexene derivative, annonaceous acetogenins, aromatic compounds and the like are separated and obtained.
The Dasymaschalon rostratum Merr is a plant of the genus soapcap of Annonaceae (Annonaceae), is a shrub or small tree growing in mountain thin forest, is mainly distributed in India, Philippine and subtropical areas of China, and is mainly used for treating diseases such as malaria and rheumatic ostealgia in folks. The plants of the genus have 3 types in China, namely yellow flower soapcap flower (D.sootense), fruit soapcap flower (D.rostratum) and soapcap flower (D.trichophorum), and are distributed in the southern Hainan region, the southwest of the Guangdong region and the like. According to the literature report, the saponaria plants are rich in alkaloid, flavone, cyclohexene derivative, annonaceous acetogenins, aromatic compounds and the like, and show biological activities such as antibiosis and tumor resistance, but the chemical components and the biological activities of the rostellularia saponaria roots are not reported.
Aristolochia lactam is a typical chemical component in saponaria plants, and the research on the chemical component and the pharmacological action is widely concerned by scholars at home and abroad. The aristololactam compound has better cytotoxic activity, antibacterial activity, antioxidation activity, antimalarial activity, anti-inflammatory activity, platelet aggregation resistance and other biological activities. In order to find better monomer compounds with biological activity, the aristolochialactam-rich dasymaschalon rostratum is systematically separated, so that a better basis is provided for the future research of the saponaria.
Disclosure of Invention
The invention aims to solve the technical problem of providing aristololactam compounds containing one hydroxyl group and a preparation method and application thereof.
The technical scheme for realizing the aim of the invention is that the aristolochia lactam compound has a structure shown in a formula A:
the preparation method of the aristololactam compound as shown in the formula A comprises the following steps:
firstly, extracting an extract: drying root of Gleditsia rostrata in the shade, pulverizing, soaking in ethanol solution at room temperature, and concentrating the ethanol solution to obtain ethanol extract.
② extraction of plant extract: and (3) dispersing the crude extract extracted by the ethanol in distilled water, extracting by using ethyl acetate, combining the extraction solutions, and carrying out reduced pressure distillation and concentration to obtain the total extract of the ethyl acetate part.
Mixing the ethyl acetate extract obtained in the step II, separating by silica gel column chromatography, and performing petroleum ether: separating with ethyl acetate (100: 0-50: 50, V/V) and chloroform-methanol (100: 0-0: 100, V/V) mixed solvent at increasing concentration, collecting distilled components at 500mL each time, detecting by TLC, and combining similar components to obtain 12 components Fr.1-Fr.12.
And fourthly, for the Fr.7 component obtained in the third step, separating the Fr.7 component through a normal phase silica gel column (200 meshes and 300 meshes), and using petroleum ether: gradient eluting with ethyl acetate (1: 0-0: 1, V/V) to obtain 9 components (Fr.7-1-Fr.7-9).
And for the Fr.7-5 component, performing high performance liquid chromatography separation on Fr.7-5, and using acetonitrile-water as a mobile phase to obtain the compound A.
An aristololactam compound, which has a structure shown in a formula B:
a preparation method of aristololactam compound shown in formula B comprises the following steps:
firstly, extracting an extract: drying root of Gleditsia rostrata in the shade, pulverizing, soaking in ethanol solution at room temperature, and concentrating the ethanol solution to obtain ethanol extract.
② extraction of plant extract: dispersing the crude extract extracted by the ethanol in distilled water, extracting by using ethyl acetate, combining the extraction liquids, and carrying out reduced pressure distillation and concentration to obtain the total extract of the ethyl acetate part.
Mixing the ethyl acetate extract obtained in the step II, separating by silica gel column chromatography, and performing petroleum ether: separating with ethyl acetate (100: 0-50: 50, V/V) and chloroform-methanol (100: 0-0: 100, V/V) mixed solvent at increasing concentration, collecting distilled components at 500mL each time, detecting by TLC, and combining similar components to obtain 12 components Fr.1-Fr.12.
And fourthly, for the Fr8 component obtained in the third step, Fr.8 is separated by a normal phase silica gel column (200 meshes and 300 meshes), and petroleum ether: gradient elution with ethyl acetate (1: 0-0: 1, V/V) to obtain 7 components (Fr.8-1-Fr.8-7).
For the Fr.8-2 component, Fr.8-2 was separated by high performance liquid chromatography using acetonitrile-water as the mobile phase to give Compound B (5.9 mg).
An application of aristololactam compound as shown in formula B in preparing medicines for resisting bacillus cereus.
An aristololactam compound, the structure of which is shown as formula C:
a preparation method of aristololactam compound shown in formula C comprises the following steps:
firstly, extracting an extract: drying root of Gleditsia rostrata in the shade, pulverizing, soaking in ethanol solution at room temperature, and concentrating the ethanol solution to obtain ethanol extract.
② extraction of plant extract: dispersing the crude extract extracted by the ethanol in distilled water, extracting by using ethyl acetate, combining the extraction liquids, and carrying out reduced pressure distillation and concentration to obtain the total extract of the ethyl acetate part.
Mixing the ethyl acetate extract obtained in the step II, separating by silica gel column chromatography, and performing petroleum ether: separating with ethyl acetate (100: 0-50: 50, V/V) and chloroform-methanol (100: 0-0: 100, V/V) mixed solvent at increasing concentration, collecting distilled components at 500mL each time, detecting by TLC, and combining similar components to obtain 12 components Fr.1-Fr.12.
And fourthly, for the Fr.7 component obtained in the third step, separating the Fr.7 component through a normal phase silica gel column (200 meshes and 300 meshes), and using petroleum ether: gradient eluting with ethyl acetate (1: 0-0: 1, V/V) to obtain 9 components (Fr.7-1-Fr.7-9).
And for the Fr.7-5 component, performing high performance liquid chromatography separation on Fr.7-5, and using acetonitrile-water as a mobile phase to obtain a compound C.
An application of aristololactam compound as shown in formula C in preparing medicines for resisting bacillus cereus.
The invention has the positive effects that: (1) the invention separates three new aristolochia lactam compounds from the root of the rostral fruit saponaria robusta, namely, aristolochia lactam with 4 methoxyl groups and 1 hydroxyl group (the hydroxyl group is at the 7 position and is called compound A), aristolochia lactam with 3 methoxyl groups and 1 hydroxyl group (the hydroxyl group is at the 4 position and is called compound B), aristolochia lactam with 4 methoxyl groups and 1 hydroxyl group (the hydroxyl group is at the 4 position and is called compound C), and the compound A and the compound C are isomers. Wherein the compound B and the compound C have obvious antibacterial activity on the bacillus cereus.
(2) The aristolochia lactam compound disclosed by the invention is simple in preparation process, is obtained by separating an ethyl acetate extraction part of an ethanol extract of the seed of the comfrey, and provides a practical basis for utilization and development of the saponaria plant.
Drawings
FIG. 1 is a drawing of Compound A1H NMR(400MHz,DMSO-d6) A spectrum;
FIG. 2 is a drawing of Compound A13C NMR(100MHz,DMSO-d6) A spectrum;
FIG. 3 shows HSQC (100MHz, DMSO-d) for Compound A6) A spectrum;
FIG. 4 shows HMBC (100MHz, DMSO-d) of Compound A6) Performing spectroscopy;
FIG. 5 is a HR-ESI-MS plot of Compound A;
FIG. 6 is a drawing of Compound B1H NMR(400MHz,Acetone-d6) A spectrum;
FIG. 7 is a drawing of Compound B13C NMR(100MHz,Acetone-d6) A spectrum;
FIG. 8 shows HSQC (100MHz, Acetone-d) of Compound B6) A spectrum;
FIG. 9 shows HMBC (100MHz, Acetone-d) of Compound B6) A spectrum;
FIG. 10 is a drawing of Compound B1H-1HCOSY(100MHz,Acetone-d6) A spectrum;
FIG. 11 is a HR-ESI-MS plot for Compound B;
FIG. 12 is a drawing of Compound C1H NMR(400MHz,DMSO-d6) A spectrum;
FIG. 13 is of Compound C13C NMR(100MHz,DMSO-d6) Performing spectroscopy;
FIG. 14 is HSQC (100MHz, DMSO-d) for Compound C6) A spectrum;
FIG. 15 shows HMBC (100MHz, DMSO-d) of Compound C6) Performing spectroscopy;
FIG. 16 is a HR-ESI-MS plot for Compound C.
Detailed Description
The aristolochia lactam compound is prepared by using the dasyma rostratum collected from the overlord mountain in Changjiang county of Hainan in 2017 for 1 month, and is identified as the root of annonaceae saponaria plant, namely dasyma rostratum Merr (D.rostratum Merr.) by professor Zhongjun core of Life sciences academy of southern Hainan university, and the plant sample is placed in a sample chamber of a key laboratory of the tropical medicinal plant chemical education department of southern Hainan university.
(example 1)
This example is a process for the preparation of compound A, B, C, comprising the steps of:
firstly, extracting an extract: drying root of Gleditsia rostrata in the shade, pulverizing, soaking in 90% (V/V) ethanol solution at room temperature for 7 days/time for 3 times, and concentrating the ethanol solution to obtain ethanol extract.
② extraction of plant extract: dispersing the crude extract extracted by the ethanol of the step I90% (V/V) in 1L of distilled water, extracting by using ethyl acetate, and extracting for 3-5 times; and after the extraction layer has no color, combining the extraction liquid of each time, and carrying out reduced pressure distillation and concentration to obtain the total extract of the ethyl acetate part.
③ mixing the ethyl acetate extract (37.1g) obtained by the extraction in the step II, separating the mixture by silica gel column chromatography (100-200 meshes), and using petroleum ether: the concentration of a mixed solvent of ethyl acetate (100: 0-50: 50, V/V) and chloroform-methanol (100: 0-0: 100, V/V) was gradually increased for separation, and 500mL of the distillate was collected. Detection by TLC and combination of similar fractions gave 12 fractions Fr.1 to Fr.12.
And fourthly, for the Fr.7 component obtained in the third step, separating the Fr.7 component through a normal phase silica gel column (200 meshes and 300 meshes), and using petroleum ether: gradient eluting with ethyl acetate (1: 0-0: 1, V/V) to obtain 9 components (Fr.7-1-Fr.7-9).
For Fr.7-5 component, Fr.7-5 is separated by high performance liquid chromatography with acetonitrile-water (75:25) as mobile phase at flow rate of 3 mL/min-1Compound A (5.7mg), C (26.4mg) was obtained.
Fifthly, for the Fr8 component obtained in the third step, Fr.8 is separated by a normal phase silica gel column (200 meshes and 300 meshes), and petroleum ether: gradient eluting with ethyl acetate (1: 0-0: 1, V/V) to obtain 7 components (Fr.8-1-Fr.8-7).
For Fr.8-2 component, Fr.8-2 is separated by high performance liquid chromatography with acetonitrile-water (8:92) as mobile phase at flow rate of 3 mL/min-1Compound B (5.9mg) was obtained.
Compound a is a tan powder, readily soluble in DMSO.
The structural formula of compound a is as follows:
the structural characterization spectra of compound a are shown in fig. 1 to 5.
The NMR model used for the analysis was Bruker AV-400MHz (Bruker, Switzerland); infrared spectrometer model Avatar360 (Nicolet corporation, usa); a high resolution mass spectrometer model Varian 7.0T FTICR-MS; mass spectrometer model Finnigan-MAT-95-MS; the same applies below.
The analysis was as follows:
FIG. 5 shows HR-ESI-MS M/z 356.1128[ M + H ]]+(calculated 356.1129), confirming that Compound A has the formula C19H17O6. Infrared data indicate the presence of hydroxyl groups in the compound (3419 cm)-1) Carbonyl group (1675 cm)-1) And benzene rings (1548,1462,1255 and 1098 cm)-1) And the like.
Of Compound A1H NMR and13the C NMR data are shown in Table 1 below.
TABLE 1 preparation of Compound A1H NMR and13c NMR data (400/100MHz, DMSO-d)6)
The compound13The high field region of the C NMR spectrum shows 4 methoxy carbon signals, the rest 15 carbon signals are all in the low field region, and one amide carbonyl carbon signal delta is includedC166.3, typical aristololactam skeleton. In addition to this, the present invention is,1in the H NMR spectrum, 3 aromatic ring or heteroaromatic ring hydrogen signals delta are shown in a low field regionH8.56(1H, s, H-5),7.28(1H, s, H-8) and 7.06(1H, s, H-9), 1 azino-hydrogen signal δH10.82(1H, s, N-H); the high field region shows 4 methoxy hydrogen signals deltaH 4.34(3H,s,2-OCH3),4.11(3H,s,4-OCH3),3.94(3H,s,6-OCH3) And 3.90(3H, s, 3-OCH)3). Of comparative Compound A1H NMR and13c NMR data was compared with known aristolactam enterocarpam III (Compound D, formula: R1＝R2＝R3＝R5＝OCH3，R4＝R6＝H)，The nuclear magnetic data of the two are very similar, and the compound A has only one less aromatic proton signal. Furthermore, it can be seen in the HMBC spectra that H-5 is associated with 147.2(C-7),115.7(C-4a) and 128.8(C-8a), H-8 is associated with 146.7(C-6),119.0(C-4b) and 104.9(C-9), and H-9 is associated with 113.1(C-8),119.0(C-4b),123.7(C-10a) and 132.99 (C-10). Based on the above information, the structure of the compound was identified as 7-hydroxy-2, 3, 4, 6-tetramethoxy substituted aristolactam.
The compound B is yellow needle crystal (Acetone), and is easily dissolved in organic solvents such as Acetone, methanol and the like.
The structural formula of compound B is as follows:
the structural characterization spectra of compound B are shown in fig. 6-11, and analyzed as follows:
HR-ESI-MS m/z:326.1023[M+H]+(calculated 326.1023) identifying the compound as C18H15NO5. Infrared data indicate the presence of hydroxyl groups (3437 cm) in the compound-1) Carbonyl group (1697 cm)-1) And benzene rings (1620,1419,1248 and 1070 cm)-1) And the like.
Of compounds B1H NMR and13the C NMR data are shown in Table 2 below.
TABLE 2 preparation of Compound B1H NMR and13c NMR data (400/100MHz, Acetone-d6)
The compound13The high field region of the C NMR spectrum shows 3 methoxy carbon signals, the rest carbon signals are all in the low field region, and the signals comprise an amide carbonyl carbon signal deltaC167.2 typical Aristolochia lactamAnd (3) a framework. In addition to this, the present invention is,1in the H NMR spectrum, 4 aromatic ring or heteroaromatic ring hydrogen signals delta are shown in a low field regionH8.79(1H, d, J ═ 2.4Hz, H-5),7.82(1H, d, J ═ 8.8Hz, H-8),7.19(1H, dd, J ═ 2.4Hz,8.8, H-7) and 7.16(1H, s, H-9), 1 azino-hydrogen signal δH9.77(1H, s, N-H); the high field region shows 3 methoxy hydrogen signals deltaH 4.48(3H,s,2-OCH3),4.18(3H,s,3-OCH3) And 3.97(3H, s, 6-OCH)3)。
In the HMBC spectrum, H-5 is associated with C-6, C-7 is associated with C-8a, H-7 is associated with C-5(109.1), C-6(158.3) is associated with C-8a (129.1), H-8 is associated with C-6(158.3), C-7(116.8), C-9(104.8) and C-8a (129.1), H-9 is associated with C-8(130.5), C-10a (123.4) and C-10(133.9), and it can be determined that C-6 is associated with a methoxy group. GIAO calculation was performed on the compound to finally obtain NMR values of 3 structures, and the experimental values were compared with the calculated chemical shift values, and when the hydroxyl group was bonded to C-4, the mean square deviation value of the calculated values and the experimental values was the smallest. Based on the above information, the structure of the compound was identified as 4-hydroxy-2, 3, 6-trimethoxy substituted aristolactam.
Compound C was a tan powder. Is easily dissolved in DMSO.
The structural formula of compound C is as follows:
the structural characterization spectra of compound C are shown in fig. 12-16, analyzed as follows:
HR-ESI-MS m/z:356.1128[M+H]+(calculated 356.1129) and the molecular formula of the compound was determined to be C19H17NO6. Infrared data indicate the presence of hydroxyl groups in the compound (3415 cm)-1) Carbonyl group (1667 cm)-1) And benzene rings (1522,1458,1236 and 1088 cm)-1) And the like.
Of compound C1H NMR and13the C NMR data are shown in Table 3 below.
TABLE 3 preparation of Compound 41H NMR and13c NMR data (400/100MHz, DMSO-d)6)
Of compound C13The low field region in the C NMR spectrum shows a signal of 15 carbons, including a signal of one amide carbonyl carbon, deltaC166.2, typical aristololactam skeleton. In addition to this, the present invention is,1in the H NMR spectrum, the low field region shows 3 aromatic ring or heteroaromatic ring hydrogen signals deltaH8.52(1H, s, H-5),7.45(1H, s, H-8) and 7.17(1H, s, H-9), 1 azino-hydrogen signal δH10.82(1H, s, N-H), 4 methoxy hydrogen signals delta appear in the high field regionH 4.35(3H,s,2-OCH3),4.08(3H,s,3-OCH3),3.91(3H,s,7-OCH3) And 3.89(3H, s, 6-OCH)3). Compare it1H NMR and13the C NMR data is compared with that of compound B, compound C, which has only one more methoxy signal. In the HMBC spectra, H-5 is seen to correlate with C-6(145.7), C-7(148.0), C-4a (115.3) and C-8a (127.6), H-8 is seen to correlate with C-9(105.5), C-4b (120.1), C-6(145.7) and C-7(148.0), and H-9 is seen to correlate with C-8(109.8), C-10(132.2), C-4b (120.1) and C-10a (124.0). Based on the above information, the structure of the compound is identified as 4-hydroxy-2, 3,6, 7-tetramethoxy substituted aristololactam.
(test examples, antibacterial Activity test)
1. Experimental Material
Test bacteria: 5 kinds of human pathogenic bacteria, which are respectively: tetragenococcus (Micrococcus tetragenous), Bacillus cereus (Bacillus cereus), Bacillus subtilis (Bacillus subtilis), Staphylococcus albus (Staphylococcus albus), and Escherichia coli (Escherichia coli).
A sample to be tested: compound A, B, C.
Experimental apparatus and reagents: 96-well plate, conical flask, alcohol lamp, clean bench, enzyme-labeling instrument (ELx800), pipettors with various measuring ranges, inoculating needle, high-temperature sterilizing pot, culture dish, constant-temperature oscillator, and culture medium constant-temperature incubator.
2. Experimental methods
The test method comprises the following steps: the method is commonly used for the test of the bacteriostatic activity of sensitive drugs or new drugs on human pathogenic bacteria by adopting a microdilution method, has simple and convenient operation method, and can be used for a large number of bacteriostatic tests. Generally, a nutrient broth culture medium is used, activated human pathogenic bacteria are inoculated into the culture medium to prepare bacterial liquid, and a medicine to be detected is dissolved in DMSO to prepare 1 mg/mL. Diluting a 96-well plate line by a double-concentration descending dilution method, wherein the dilution degree is 1:500-1: 1000; quantitatively adding the diluted culture solution containing the bacteria into each hole of a 96-hole plate respectively; then adding diluted bacteria solution, reserving two holes as a reference, adding only the culture medium in one hole and adding only the bacteria solution in the other hole, shaking and mixing uniformly after dilution, placing a 96-hole plate in a constant-temperature incubator at 37 ℃ for culturing for 20h, measuring the absorbance at 630nm by using an enzyme-labeling instrument, and measuring the value of the Minimum Inhibitory Concentration (MIC).
3. Experimental procedure
(1) Preparation of pathogenic strains: and taking out the 5 pathogenic bacteria from the ultralow temperature refrigerator respectively, and activating for later use.
(2) Preliminary screening of the compounds: preparing culture medium, performing two sets of parallel primary screening for each kind of bacteria, inoculating each kind of pathogenic bacteria into each culture medium, and culturing in constant temperature incubator for 6-12 hr. Diluting the cultured pathogenic bacteria with a culture solution (the dilution gradient is 1:500-1:1000), and quantitatively adding the diluted culture solution containing the bacteria into each hole of a 96-hole plate respectively; preparing a sample to be detected into 1mg/mL, respectively quantitatively adding the sample to be detected into the first row of holes, and then diluting the sample in an equal concentration gradient manner. After the addition, the cells were incubated at 37 ℃ in a constant temperature incubator, and then the absorbance of each well was measured at 630nm using a microplate reader.
(3) Testing of minimum inhibitory concentration: diluting the cultured pathogenic bacteria with a culture solution, wherein the dilution gradient is 1:500-1: 1000; quantitatively adding the diluted culture solution containing bacteria into each first row of wells of a 96-well plate respectively; then each sample is added to the first row of wells, and then sequentially diluted in an isoconcentration gradient. After the addition, the cells were incubated at 37 ℃ in a constant temperature incubator, and then the absorbance of each well was measured at 630nm using a microplate reader.
4. The results of the experiments are shown in Table 4 below.
Table 4 results of antibacterial Activity test of some Compounds
Note: ciprofloxacin was the positive control.
From the test results, it can be seen that compounds B and C have significant bacteriostatic activity against Bacillus cereus.
Claims (3)
1. A preparation method of aristololactam compound has a structure shown in formula A,
firstly, extracting an extract: drying root of Gleditsia rostrata in the shade, pulverizing, soaking in ethanol solution at room temperature, and concentrating the ethanol solution to obtain ethanol extract;
② extraction of plant extract: dispersing the crude extract extracted by the ethanol in distilled water, extracting by using ethyl acetate, combining the extraction solutions, and carrying out reduced pressure distillation and concentration to obtain a total extract of an ethyl acetate part;
③ mixing the ethyl acetate extract obtained by the extraction in the step II, and separating the mixture by silica gel column chromatography, wherein the concentration of the ethyl acetate extract is gradually increased by petroleum ether-ethyl acetate and chloroform-methanol mixed solvent for separation, the volume ratio of the petroleum ether to the ethyl acetate eluent is 100: 0-50: 50, and the volume ratio of the chloroform to the methanol eluent is 100: 0-0: 100;
collecting distilled components by 500mL each time, detecting by TLC, and combining similar components to obtain 12 components Fr.1-Fr.12;
and fourthly, for the Fr.7 component obtained in the third step, separating the Fr.7 component by using a normal phase silica gel column, and performing separation by using petroleum ether with the volume ratio of 1: 0-0: 1: gradient elution with ethyl acetate to obtain 9 components Fr.7-1-Fr.7-9;
and for the Fr.7-5 component, performing high performance liquid chromatography separation on Fr.7-5, and using acetonitrile-water as a mobile phase to obtain the compound A.
2. A preparation method of aristololactam compound has a structure shown in formula B,
firstly, extracting an extract: drying root of Gleditsia rostrata in the shade, pulverizing, soaking in ethanol solution at room temperature, and concentrating the ethanol solution to obtain ethanol extract;
② extracting the plant extract: dispersing the crude extract extracted by the ethanol in distilled water, extracting by using ethyl acetate, combining the extraction solutions, and carrying out reduced pressure distillation and concentration to obtain a total extract of an ethyl acetate part;
③ mixing the ethyl acetate extract obtained by the extraction in the step II, and separating the mixture by silica gel column chromatography, wherein the concentration of the ethyl acetate extract is gradually increased by petroleum ether-ethyl acetate and chloroform-methanol mixed solvent for separation, the volume ratio of the petroleum ether to the ethyl acetate eluent is 100: 0-50: 50, and the volume ratio of the chloroform to the methanol eluent is 100: 0-0: 100;
collecting distilled components by 500mL each time, detecting by TLC, and combining similar components to obtain 12 components Fr.1-Fr.12;
and fourthly, for the Fr8 component obtained in the third step, Fr.8 is separated by a normal phase silica gel column, and petroleum ether with the volume ratio of 1: 0-0: 1 is used: gradient elution is carried out on ethyl acetate to obtain 7 components Fr.8-1 to Fr.8-7;
and for the Fr.8-2 component, performing high performance liquid chromatography separation on the Fr.8-2 component by using acetonitrile-water as a mobile phase to obtain a compound B.
3. A preparation method of aristololactam compound has a structure shown in formula C,
firstly, extracting an extract: drying root of Gleditsia rostrata in the shade, pulverizing, soaking in ethanol solution at room temperature, and concentrating the ethanol solution to obtain ethanol extract;
② extracting the plant extract: dispersing the crude extract extracted by the ethanol in distilled water, extracting by using ethyl acetate, combining the extraction solutions, and carrying out reduced pressure distillation and concentration to obtain a total extract of an ethyl acetate part;
③ mixing the ethyl acetate extract obtained by the extraction in the step II, and separating the mixture by silica gel column chromatography, wherein the concentration of the ethyl acetate extract is gradually increased by petroleum ether-ethyl acetate and chloroform-methanol mixed solvent for separation, the volume ratio of the petroleum ether to the ethyl acetate eluent is 100: 0-50: 50, and the volume ratio of the chloroform to the methanol eluent is 100: 0-0: 100;
collecting distilled components by 500mL each time, detecting by TLC, and combining similar components to obtain 12 components Fr.1-Fr.12;
and fourthly, for the Fr.7 component obtained in the third step, separating the Fr.7 component by using a normal phase silica gel column, and performing separation by using petroleum ether with the volume ratio of 1: 0-0: 1: gradient elution is carried out on the concentration of ethyl acetate to obtain 9 components Fr.7-1 to Fr.7-9;
and for the Fr.7-5 component, performing high performance liquid chromatography separation on Fr.7-5, and using acetonitrile-water as a mobile phase to obtain a compound C.
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| Alison G. Pacheco et al..ESTUDO QUÍMICO E ATIVIDADE ANTIBACTERIANA DO CAULE DE Aristolochia esperanzae Kuntze (ARISTOLOCHIACEAE).《Quim. Nova》.2010,第33卷(第8期),第1649-1652页. * |
| Aristolactam-Type Alkaloids from Orophea enterocarpa and Their Cytotoxicities;Sanchai Nayyatip et al.;《Int. J. Mol. Sci.》;20120420;第13卷;第5010-5018页 * |
| Chemical composition, antimicrobial and antimycobacterial activities of Aristolochia triangularis Cham. from Brazil;Alessandra O. Pereira et al.;《Industrial Crops & Products》;20180525;第121卷;第461-467页 * |
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