CN112300156B - Marine-derived anti-tumor active compound and preparation method and application thereof - Google Patents
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Abstract
The invention relates to the technical field of marine organisms and medicines, in particular to an anti-tumor active compound separated from marine sponge Aaptos suberioides, a preparation method and anti-tumor application thereof. The anti-tumor active compound is an aaptamine compound separated from sponge Aaptos subeitides for the first time, the molecular formula and the structure of the compound are confirmed by spectrum data such as nuclear magnetic resonance, mass spectrum and the like, and the compound is simple and easy to extract, simple in structure and easy to artificially synthesize. Meanwhile, through test of a CCK8 method, the compound has obvious inhibitory activity on lung cancer cells H1299, lung cancer cells H520, stomach cancer cells SCG7901, nasopharyngeal carcinoma cells CNE-2 and colon cancer cells SW480, and can be used as a lead compound for research and development of antitumor drugs. The invention provides scientific basis for developing and utilizing marine biological resources and anti-tumor new drugs in China.
Description
Technical Field
The invention relates to the technical field of marine organisms and medicines, in particular to an anti-tumor active compound separated from marine sponge Aaptos suberioides, and a preparation method and application thereof.
Background
Tumors are a global problem that endangers human life and health, and in recent years, have been on a global rising trend. It is expected that in the next 20 years, there will be 2200 million new cancer cases per year and 1300 million deaths from concurrent cancer will occur. Therefore, the development of effective anticancer drugs remains a primary task for tumor therapy. The marine anti-tumor natural product has a leading position in the research of marine medicines. Data from the us NCI indicate that more than 1% of compounds in the ocean have anti-tumor activity, while only 0.01% in terrestrial plants. Among them, the secondary metabolites derived from the sponge play an important role in the development of anti-tumor drugs.
The sponge Aaptos suberioides belongs to the class Demospongiae (Demospongiae), the order Topongiae (Hadromerida), the family Debeaconidae (Suberidae), the genus Aaptos, and its main characteristic component is aaptamine alkaloid. The alkaloid has significant biological activities of resisting tumor, virus, bacteria and oxidation. Therefore, the active ingredients in the sponge Aaptos subeitoides are deeply researched, aaptamine alkaloid with anti-tumor activity is excavated, and the development and utilization of the sponge and the research and development of new anti-tumor drugs are facilitated.
Disclosure of Invention
The invention aims at providing a marine antitumor active compound, a preparation method of the antitumor active compound and an application of the antitumor active compound in preparation of antitumor drugs.
The first purpose of the invention is realized by adopting the following technical scheme:
1. an anti-tumor active compound of marine origin, characterized in that: the compound is separated from sponge Aaptos subeitides, and has a molecular formula of C18H19N3O4The structural formula is as follows:
the compound was named:
3-(N-5-methyl pentanoate)aminodemethyl(oxy)aaptamine。
the second purpose of the invention is realized by adopting the following technical scheme:
the preparation method of the anti-tumor active compound comprises the following steps:
1. raw material treatment: crushing the frozen sponge sample by a crusher, and dynamically cold-soaking and extracting the crushed sponge sample for 3 times by methanol at room temperature, wherein the soaking time is 5 days; mixing the extractive solutions, and concentrating under reduced pressure at 40 deg.C; dissolving and desalting for 3 times with anhydrous methanol to obtain extract;
2. silica gel reduced pressure column chromatography: dissolving the extract in 1.5-3 times of pure methanol, mixing with 1-3 times of 100-mesh 200-mesh silica gel, and loading on silica gel decompression column; gradient elution is carried out by respectively using petroleum ether ethyl acetate solution with the volume ratio of petroleum ether to ethyl acetate being 100:0, 50:1, 30:1, 20:1, 10:1, 5:1, 2:1 and 1:1 and dichloromethane methanol solution with the volume ratio of dichloromethane to methanol being 20:1, 10:1, 5:1, 2:1, 1:1 and 0:1, eluent of each part is respectively collected and concentrated, TLC thin-layer chromatography is used for monitoring and merging the same parts;
3. ODS column chromatography: taking the component eluted by the dichloromethane methanol solution with the volume ratio of 20:1 in the step 2, passing through an ODS column, performing gradient elution by using methanol solutions with the volume ratios of methanol to water of 1:4, 3:7, 4:6, 5:5 and 6:4 respectively, collecting the eluents of all the parts respectively, concentrating, monitoring by TLC thin-layer chromatography, and combining the same parts;
4. high performance liquid chromatography separation: and (3) taking the components eluted by the methanol solution with the volume ratio of 4:6 in the step (3), performing high performance liquid analysis, and preparing the compound by using an ODS C18 column, wherein the retention time is 23.7 minutes.
Preferably: in the step 2, the filler silica gel of the silica gel decompression column is 200-300 meshes.
Preferably: in the step 4, the ODS C18 column adopts a YMC ODS C18 column, the model is 10 x 250mm, the filler particle size is 5 mu m, the mobile phase is acetonitrile/water 40:60v/v, and the flow rate is 1.5 mL/min.
The third purpose of the invention is realized by adopting the following technical scheme:
the application of the anti-tumor active compound in preparing anti-tumor drugs, specifically: the compound can be used as a lead compound for research and development of antitumor drugs for inhibiting proliferation of lung cancer cells H1299, lung cancer cells H520, gastric cancer cells SCG7901, nasopharyngeal carcinoma cells CNE-2 and colon cancer cells SW 480.
Has the advantages that: the anti-tumor active compound is an aaptamine compound separated from sponge Aaptos subeitides for the first time, the molecular formula and the structure of the compound are confirmed by spectrum data such as nuclear magnetic resonance, mass spectrum and the like, and the compound is simple and easy to extract, simple in structure and easy to artificially synthesize. Meanwhile, through test of a CCK8 method, the compound has obvious inhibitory activity on lung cancer cells H1299, lung cancer cells H520, stomach cancer cells SCG7901, nasopharyngeal carcinoma cells CNE-2 and colon cancer cells SW480, and can be used as a lead compound for research and development of antitumor drugs. The invention provides scientific basis for developing and utilizing marine biological resources and anti-tumor new drugs in China.
Drawings
FIG. 1 is a process flow diagram of a method for preparing a compound of the present invention;
FIG. 2 shows NMR of the compound of the present invention1H NMR) spectrum;
FIG. 3 shows NMR spectra of compounds of the present invention13C NMR) spectrum;
FIG. 4 shows NMR of the compound of the present invention1H-1H COSY) spectrum;
FIG. 5 is a nuclear magnetic resonance Hydrogen (HMQC) spectrum of a compound of the invention;
FIG. 6 is a hydrogen nuclear magnetic resonance (HMBC) spectrum of a compound of the present invention;
FIG. 7 is a high resolution mass (HRESIMS) spectrum of a compound of the invention.
Detailed Description
The invention is further described with reference to the following figures and detailed description.
Example (b):
the marine-derived anti-tumor active compound described in this example was isolated from sponge Aaptos suberioides and has a molecular formula of C18H19N3O4The structural formula is as follows:
the compound was named:
3-(N-5-methyl pentanoate)aminodemethyl(oxy)aaptamine。
the sponges Aaptos subeititides were collected from the sea area of seisha Yongxing island in 2012 and stored frozen at-20 ℃.
The preparation method of the anti-tumor active compound comprises the following steps:
1. raw material treatment: crushing a sponge sample with the wet weight of 2.5kg which is preserved by freezing by a crusher, and dynamically cold-soaking and extracting for 3 times by methanol at room temperature, wherein the soaking time is 5 days; mixing the extractive solutions, and concentrating under reduced pressure at 40 deg.C; dissolving and desalting with anhydrous methanol for 3 times to obtain extract (Aaptos subeitides crude extract);
2. silica gel reduced pressure column chromatography: dissolving the extract in 1.5-3 times of pure methanol, mixing with 1-3 times of 100-mesh silica gel of 200 meshes, and loading on silica gel decompression column (the filler silica gel of the silica gel decompression column is 200-mesh 300 meshes); gradient elution is carried out by respectively using petroleum ether ethyl acetate solution with the volume ratio of petroleum ether to ethyl acetate being 100:0, 50:1, 30:1, 20:1, 10:1, 5:1, 2:1 and 1:1 and dichloromethane methanol solution with the volume ratio of dichloromethane to methanol being 20:1, 10:1, 5:1, 2:1, 1:1 and 0:1, eluent of each part is respectively collected and concentrated, TLC thin-layer chromatography is used for monitoring and merging the same parts;
3. ODS column chromatography: taking the component eluted by the dichloromethane methanol solution with the volume ratio of 20:1 in the step 2, passing through an ODS column, performing gradient elution by using methanol solutions with the volume ratios of methanol to water of 1:4, 3:7, 4:6, 5:5 and 6:4 respectively, collecting the eluents of all the parts respectively, concentrating, monitoring by TLC thin-layer chromatography, and combining the same parts;
4. high performance liquid chromatography separation: and (3) taking the components eluted by the methanol solution with the volume ratio of 4:6 in the step (3), performing high performance liquid analysis, and preparing the compound by using an ODS C18 column, wherein the retention time is 23.7 minutes. Preferably, the ODS C18 column is YMC ODS C18 column, model is 10 × 250mm, filler particle size is 5 μm, mobile phase is acetonitrile/water 40:60v/v, and flow rate is 1.5 mL/min.
Structural analysis of Compound
The prepared antitumor active compound is taken to carry out detection and analysis on spectral data such as mass spectrum, infrared spectrum, ultraviolet spectrum, nuclear magnetic resonance and the like, and the result is as follows: the compound is orange powder, and is easily soluble in methanol; dark spots appear under an ultraviolet lamp with the wavelength of 254 nm; UV spectrum (MeOH) has characteristic absorption peaks at 210, 250, 280 and 390 nm; the 10% ethanol sulfate developed red. The high resolution mass spectrum gives the excimer ion peak M/z 342.1439[ M + H ]]+(calculated 342.1448). Determining the formula of the compound as C18H19N3O4，The unsaturation degree was 11. The compound is presumed to be aaptamine alkaloid according to TLC and HPLC ultraviolet absorption characteristics.
Analysis of compounds1H NMR data, giving 4 signals of aromatic protons, deltaH 8.86(1H，d，J＝4.4Hz)，δH8.40(1H，s)，δH 7.76(1H，d，J＝4.5Hz)，δH7.03(1H, s), two methoxy proton signals δH 3.87(3H，s)，δH3.56(3H, s), two hydrogen signals Δ to NH3.55(2H, m) and high field region 3 groups CH2Signal deltaH 2.37(2H，t，J＝7.3Hz)，δH 1.69(2H，m)，δH 1.63(2H，m)。13C NMR data show the two carbonyl carbon signals deltac 174.3，δc173.3, 4 olefin methine signals deltac150.3, 129.8, 122.0, 106.5, high field region 4 methylene signals deltac41.3, 32.6, 27.4, 21.6, 2 methoxy signals deltacQuaternary carbon signals δ of 55.6, 51.0 and 6 olefinsc157.3, 144.4, 135.5, 135.4, 132.9, 117.6, characteristic H and C spectra signals, which suggest that the compound is an aaptamine alkaloid.
The carbon and hydrogen of the compound are assigned by HMQC, and delta is obtained from the H-H COSY spectrumH8.42 and deltaH3.55 correlation, δH3.55 and deltaH 1.69Correlation, deltaH1.69 and deltaH1.63 correlation, δH1.63 and 2.37 related signals, connecting-NH-CH2-CH2-CH2-CH2A fragment of (a). According to deltaH8.86 and deltaH7.76 correlation signals, with the-CH-CH-fragment being ligated. In HMBC spectrum, δH2.37 and deltac135.5, 135.4 correlation, deltaH8.40 and deltac135.5, 132.9 correlation, δH7.76 and deltac106.8, 117.6 correlation, δH7.03 and deltac117.6, 122.2, 157.3, 174.3 correlation, δH3.87 and deltac157.3 correlation, deltaH8.42 and deltac144.4 correlation signals, identifying the compound as a 3-amino demethyl (oxy) aaptamine derivative containing a substituent at N-1'. Further according to the HMBC spectrogram, deltaH2.37 and deltac173.3, 21.8, 27.2, 41.5, deltaH1.69 and deltac21.8, 41.5 correlation, δH3.55 and deltac173.3 correlation, δH1.63 and deltac173.3, 27.2, 32.9, 41.5 of the signals relating to the determination of the substituent-NH-CH2-CH2-CH2-CH2-COO-CH3And determining that the substituent is attached at the N-1' position. Thus, the compound was determined to be:
3-(N-5-methyl pentanoate)aminodemethyl(oxy)aaptamine。
table 1: process for preparing compounds with antitumor activity1H and13NMR data (DMSO-d6, TMS)
| Position | δc a | δH b(J in Hz) |
| 2 | 129.8 | 8.40(1H，s) |
| 3 | 144.4 | |
| 3a | 135.5 | |
| 5 | 150.5 | 8.86(1H，J＝4.4Hz) |
| 6 | 122.2 | 7.76(1H，d，J＝4.5Hz) |
| 6a | 135.4 | |
| 7 | 106.8 | 7.03(1H，s) |
| 8 | 157.3 | |
| 9 | 174.3 | |
| 9a | 132.9 | |
| 9b | 117.6 | |
| 1′ | - | 8.42(1H，s) |
| 2′ | 41.5 | 3.55(2H，m) |
| 3′ | 27.7 | 1.69(2H，m) |
| 4′ | 21.8 | 1.63(2H，m) |
| 5′ | 32.9 | 2.37(2H，t，J＝7.3Hz) |
| 6′ | 173.3 | |
| 7′ | 51.2 | 3.55(3H，s) |
| 8′ | 55.8 | 3.87(3H，s) |
aRecorded at 150MHz；bRecorded at 600MHz。
The invention relates to an application of an anti-tumor active compound in preparing anti-tumor drugs, in particular to an application of the anti-tumor active compound in preparing anti-tumor drugs, which comprises the following steps: the compound can be used as a lead compound for research and development of antitumor drugs for inhibiting proliferation of lung cancer cells H1299, lung cancer cells H520, gastric cancer cells SCG7901, nasopharyngeal carcinoma cells CNE-2 and colon cancer cells SW 480.
Determination of antitumor Activity
1. The antitumor active compound prepared in the above example was dissolved in dimethyl sulfoxide (DMSO), and then prepared into a stock solution of 10mg/mL of antitumor active compound in a culture medium (RPMI 1640 containing 10% fetal bovine serum) and stored at-20 ℃. Immediately before use, the antitumor active compounds are diluted with the culture medium to final concentrations of 0.25mg/mL, 0.5mg/mL, 1mg/mL, 2mg/mL, 4mg/mL and 6mg/mL, respectively, and wherein the final concentration of DMSO in the test solution is controlled to be 0.01% or less at any dilution.
2. Digesting human non-small cell lung cancer cell line H1299, lung cell cancer cell line H520, human gastric cancer cell line SCG7901, human nasopharyngeal carcinoma cell line CNE-2 and human colon cancer cell line SW480 with 0.25% of pancreatin respectively, suspending in RPMI1640 culture solution containing 10% fetal calf serum, gently blowing and beating into single cell suspension for cell counting, and then diluting with the culture solution to the concentration of 50000 cells/mL.
3. Cisplatin was dissolved in DMSO, and the resulting solution was prepared into a stock solution containing 5mM cisplatin (RPMI 1640 medium containing 10% fetal bovine serum) and stored at-20 ℃. Immediately before use, the sample is diluted with the culture medium to final concentrations of 5mM, 1mM, 0.5mM, 0.25mM, 0.125mM and 0.0625mM, respectively, and the final concentration of DMSO in any diluted sample is controlled to be below 0.01%, and the sample is used as a positive control drug.
4. 100 mul of well-grown tumor cells (about 5000 cells/well) were added to each well of a 96-well culture plate, 1 mul of drugs (anti-tumor active compound and cisplatin) were added to each well after the cells were completely attached to the wall after 24 hours of culture, six duplicate wells were set in parallel for each group, and a negative control (medium and tumor cells were added, no drug was added) and a blank control (medium only, no tumor cells were added) were set. Placing at 37 ℃ in CO2Culturing at 5% concentration for 48 h. Then, 810. mu.L of CCK was added to each well, and the culture was continued for 2 to 4 hours with the absorbance value at 450nm, i.e., OD value, using a microplate reader. And calculating the cell proliferation inhibition rate. The experiment was repeated 3 times for each group of samples and the average value was taken.
Cell viability ═ 100% (OD sample-OD blank)/(OD negative control-OD blank) ×
Cell proliferation inhibition rate of 100% -cell survival rate
IC 50: the mass concentration of the medicine when the tumor cell inhibition rate is 50 percent.
The experimental results are as follows: negative control, good cell growth and no growth inhibition phenomenon, which indicates that the test method is feasible.
Table 2: IC50 value measured by test solution group
The cytotoxic activity of 5 tumor cell lines of lung cancer H1299, lung cancer H520, gastric cancer SCG7901, colon cancer SW480 and nasopharyngeal carcinoma CNE-2, which were screened against the antitumor active compounds by the CCK8 method, and the results of measurement of the half-maximal inhibitory amount (IC 50 value,. mu.g/mL) were compared with that of cisplatin (DDP), a commercial anticancer drug. The experimental result shows that the compound has stronger anti-tumor activity on lung cancer H1299, lung cancer H520 and gastric cancer SCG7901, and has application value in preparing medicaments for resisting lung cancer and gastric cancer clinically.
The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all equivalent structures made by using the contents of the present specification and the drawings can be directly or indirectly applied to other related technical fields, and are within the scope of the present invention.
Claims (4)
1. An anti-tumor active compound of marine origin, characterized in that: the compound is separated from sponge Aaptos subeitides, and has a molecular formula of C18H19N3O4The structural formula is as follows:
2. a process for the preparation of an antitumoral active compound according to claim 1, characterized in that: the method comprises the following steps:
(1) raw material treatment: crushing the frozen sponge sample by a crusher, and dynamically cold-soaking and extracting the crushed sponge sample for 3 times by methanol at room temperature, wherein the soaking time is 5 days; mixing the extractive solutions, and concentrating under reduced pressure at 40 deg.C; dissolving and desalting for 3 times with anhydrous methanol to obtain extract;
(2) silica gel reduced pressure column chromatography: dissolving the extract in 1.5-3 times of pure methanol, mixing with 1-3 times of 100-mesh 200-mesh silica gel, and loading on silica gel decompression column; gradient elution is carried out by respectively using petroleum ether ethyl acetate solution with the volume ratio of petroleum ether to ethyl acetate being 100:0, 50:1, 30:1, 20:1, 10:1, 5:1, 2:1 and 1:1 and dichloromethane methanol solution with the volume ratio of dichloromethane to methanol being 20:1, 10:1, 5:1, 2:1, 1:1 and 0:1, eluent of each part is respectively collected and concentrated, TLC thin-layer chromatography is used for monitoring and merging the same parts;
(3) ODS column chromatography: taking the component eluted by the dichloromethane methanol solution with the volume ratio of 20:1 in the step (2), passing through an ODS column, performing gradient elution by using methanol solutions with the volume ratios of methanol to water of 1:4, 3:7, 4:6, 5:5 and 6:4 respectively, collecting eluents of all parts respectively, concentrating, monitoring by TLC thin-layer chromatography, and combining the same parts;
(4) high performance liquid chromatography separation: and (4) carrying out high performance liquid analysis on the components eluted by the methanol solution with the volume ratio of 4:6 in the step (3), and preparing the compound by using an ODS C18 column, wherein the retention time is 23.7 minutes.
3. The process for the preparation of an antitumoral active compound according to claim 2, characterized in that: in the step (2), the filler silica gel of the silica gel decompression column is 200-300 meshes.
4. The process for the preparation of an antitumoral active compound according to claim 2, characterized in that: in the step (4), the ODS C18 column is YMC ODS C18 column with the model of 10X 250mm, the filler particle size of 5 μm, the mobile phase of acetonitrile/water 40:60v/v, and the flow rate of 1.5 mL/min.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107556313A (en) * | 2017-10-07 | 2018-01-09 | 扬州大学附属医院 | A kind of active component for being isolated from the red sage root and its application in cranial vascular disease is treated |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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Non-Patent Citations (4)
| Title |
|---|
| 3-(Phenethylamino)demethyl(oxy)aaptamine as an anti-dormant mycobacterial substance: Isolation, evaluation and total synthesis;Yuji Sumii 等;《Tetrahedron Letters》;20200411;第61卷(第22期);第1-4页 * |
| Cytotoxic Aaptamine Derivatives from the South China Sea Sponge Aaptos aaptos;Hao-Bing Yu 等;《Journal of Natural Products》;20140911;第77卷(第9期);第2124-2129页 * |
| Three new aaptamine derivatives from the South China Sea sponge Aaptos aaptos;Jian-Hong Gan 等;《Journal of Asian Natural Products Research》;20151224;第17卷(第2期);第1-8页 * |
| Yuan Gao 等.Total Synthesis of Aaptamine, Demethyloxyaaptamine, and Their 3‑Alkylamino Derivatives.《Organic Letters》.2019,第21卷(第5期),第1430-1433页. * |
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