Pachysandra terminalis alkaloid Pactermine Q as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to pachysandra terminalis alkaloid Pactermine Q as well as a preparation method and application thereof. The invention provides a pachysandra terminalis alkaloid Pactermine Q with anti-tumor biological activity, the compound is a new alkaloid separated from pachysandra terminalis, and the inhibition effect on human brain glioma cells is obviously better than that of temozolomide.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and more specifically, relates to a Pactermine Q alkaloid from the fruit of the jujube tree, its preparation method, and its application. Background Technology

[0002] Top-flowered bench fruit ( Pachysandraterminalis *Begonia spp.* is an evergreen plant belonging to the genus *Begonia* in the family Buxaceae. It is widely distributed in southern China, primarily in the Qinling-Bashan Mountains of Shaanxi Province. Chemical components isolated from *Begonia spp.* mainly include alkaloids, triterpenoids, and volatile oils. Modern pharmacological studies have shown that it possesses antioxidant, anti-ulcer, antitumor, antibacterial, and insecticidal activities.

[0003] Cancer is a major global health challenge, with all types posing serious health risks. It is also a leading cause of death worldwide, with millions of new cases diagnosed each year. Current treatments primarily involve immunotherapy: immune checkpoint inhibitors targeting PD-1 / PD-L1 and CTLA-4 have revolutionized NSCLC (non-small cell lung cancer) treatment, significantly improving survival rates; targeted therapy: drugs targeting specific gene mutations in NSCLC (such as epidermal growth factor receptor and ALK) have shown efficacy in certain patient populations; and drugs targeting specific gene mutations (such as KRAS and BRAF) are used for advanced colorectal cancer. However, current treatments weaken the immune system, increasing the likelihood of infection; causing skin allergies and redness; and potentially leading to autoimmune responses affecting various organs.

[0004] Gliomas are the most common pathological type of primary central nervous system tumors. Originating from neuroepithelial tissue, they have an incidence rate of 3 / 100,000–8 / 100,000, accounting for approximately 50% of all intracranial tumors. According to the WHO Classification of Tumors of the Central Nervous System (2021 edition), gliomas are reorganized into adult diffuse gliomas, pediatric diffuse low-grade and high-grade gliomas, localized astrocytic gliomas, and ependymal tumors. Among these, high-grade gliomas, especially glioblastomas (GBM), have the highest malignancy, with a 5-year survival rate of less than 5% and a median survival of less than 15 months. Surgical resection and radiotherapy / chemotherapy remain among the most important treatment methods. Emerging treatments such as gene therapy, targeted therapy, and immunotherapy are developing rapidly and can increase treatment options to some extent. However, regardless of the treatment method used, improving the postoperative quality of life and prolonging the patient's survival remains one of the most challenging problems in neurosurgery. Overall, although significant progress has been made in the treatment of lung and colon cancer, the harm caused by the immune side effects cannot be ignored. Therefore, there is an urgent need to find compounds with anti-tumor activity from traditional Chinese medicine and natural drugs. Summary of the Invention

[0005] The purpose of this invention is to provide a Pactermine Q alkaloid from the fruit of the 'Top Flower Bench Fruit' plant, its preparation method, and its application.

[0006] This invention provides a pactermine Q alkaloid from the fruit of the jujube tree, the chemical structural formula of which is as follows: .

[0007] This invention isolates a novel alkaloid compound, Pactermine Q, from the ethanol extract of the fruit of the 'Top Flower' (Prunus armeniaca). Pactermine Q is a colorless, flaky crystal with the chemical formula C. 14 H 25 NO3, specific rotation: [ α ] 20 D +27.5 ( c 0.05, MeOH), UV spectrum: UV(MeOH)λ max <200nm, Infrared spectrum: IR(KBr)ν max :3378, 2955, 2922, 1685, 1198, 1133, 1019, 717cm -1 High-resolution mass spectrometry: HR-ESI-MS: m / z 256.1918[M+H] + Experimental results showed that compound Pactermine Q had a better inhibitory effect on U87 glioma cells compared with temozolomide, with IC50 values ​​at 24h, 48h, and 72h. 50 The concentrations were 12.3 μM, 5.17 μM, and 3.86 μM, and Pactermine Q, as a chemical drug, does not have the side effect of immune response.

[0008] This invention also provides a method for preparing the alkaloid Pactermine Q from the top-flowered bench fruit, comprising the following steps: S1. Extract the fruit of the top flower by reflux with an ethanol solution of 75%~85% by volume, extract 2~4 times, and concentrate the extract to obtain the extract. S2. Mix the extract and water at a volume ratio of 0.5~1.5kg:0.5~1.5L to obtain a premix. Extract the premix with an equal volume of n-butanol. Take the n-butanol phase extract and dissolve it in 5~7 times the volume of water to obtain a solution. Adjust the pH of the solution to 1. Extract the solution 2~4 times with an equal volume of petroleum ether. Then adjust the pH of the solution to 10 and extract it 2~4 times with an equal volume of chloroform to obtain the total alkaloid extract. S3. Elute the total alkaloid extract isocratically with a semi-preparative liquid chromatography system, retaining the fraction Fr.4 with an elution time of 40-60 min. Elute Fr.4 isocratically with a semi-preparative liquid chromatography system, retaining the fraction Fr.4-1 with an elution time of 13-25 min. Elute Fr.4-1 isocratically with a semi-preparative liquid chromatography system, retaining the fraction with an elution time of 40-50 min to obtain Pactermine Q.

[0009] This invention also provides the application of Pactermine Q, an alkaloid from the fruit of the 'Top Flower Bench Fruit,' in the preparation of drugs for treating tumors.

[0010] Furthermore, the tumor includes glioblastoma.

[0011] Furthermore, the drug is prepared from the alkaloid Pactermine Q from the fruit of the jujube tree and pharmaceutically acceptable excipients.

[0012] Furthermore, the excipients are selected from any one or more of fillers, stabilizers, diluents, and adjuvants.

[0013] Furthermore, the diluent is either water or physiological saline.

[0014] The present invention also provides a drug for treating glioblastoma, the drug being a mixture of the alkaloid Pactermine Q from the fruit of *Pactermine spp.* and excipients, wherein the content of Pactermine Q in the drug is 0.1 wt% to 99 wt%.

[0015] The present invention has the following beneficial effects: The alkaloid Pactermine Q obtained from the fruit of the *Prunus cerevisiae* exhibits significant anti-glioma activity and has potential for development and application in the field of anti-glioma therapy. Attached Figure Description

[0016] Figure 1 This is the ultraviolet spectrum of compound Pactermine Q.

[0017] Figure 2 This is the infrared spectrum of compound Pactermine Q.

[0018] Figure 3 This is the proton NMR spectrum of compound Pactermine Q.

[0019] Figure 4 This is the carbon spectrum of compound Pactermine Q.

[0020] Figure 5 This is the DEPT spectrum of the compound Pactermine Q.

[0021] Figure 6 This is the HSQC spectrum of compound Pactermine Q.

[0022] Figure 7 For the compound Pactermine Q 1 H- 1 H COSY spectrum.

[0023] Figure 8 This is the HMBC spectrum of compound Pactermine Q.

[0024] Figure 9 The image shows the HR-ESI-MS spectrum of compound Pactermine Q.

[0025] Figure 10 This is the single-crystal diffraction pattern of the compound Pactermine Q.

[0026] Figure 11 The graphs show cell viability statistics, where A represents cell viability after Pactermine Q treatment, B represents TMZ cell viability, and C represents IC50 cell viability. 50 Value statistics chart.

[0027] Figure 12 This is a flow cytometry image.

[0028] Figure 13 This is a cell cycle diagram. Detailed Implementation

[0029] The present invention will now be described in detail with reference to specific embodiments, but these should not be construed as limiting the invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following embodiments can be obtained commercially unless otherwise specified.

[0030] Example 1 1. Experimental materials Top-flowered Bench Fruit: Fresh top-flowered bench fruit is dried in the shade at room temperature. The top-flowered bench fruit is collected from Taibai Mountain in Baoji, Shaanxi Province.

[0031] Extraction of extract: The fruit of the top flower was extracted by reflux with 80% ethanol (v / v) for 3 times. The extract was concentrated to obtain 1 kg of extract.

[0032] Commonly used organic solvents: dichloromethane, chloroform, methanol, ethyl acetate, petroleum ether, etc., are all industrial reagents and are used after redistillation. Other organic solvents include: chromatographic methanol, chromatographic acetonitrile, trifluoroacetic acid, and dilute hydrochloric acid. Unless otherwise specified, all reagent volumes below are volume ratios.

[0033] Commonly used reagents: DMEM high glucose medium (Meilun; MA0212), AUS GeneX fetal bovine serum (Shanghai Zhennuo; FBSSA500-S), Shanghai Saiyi Biotechnology Co., Ltd. CCK-8 assay kit (Beyotime; C0038), Annexin V-FITC apoptosis assay kit (Beyotime; C1062), cell cycle and apoptosis assay kit (Beyotime; C1052).

[0034] Commonly Used Instruments: AVANCE 400 NMR Spectrometer (Burker, Switzerland); Applied Photophysics Circular Dichroism Spectrometer (Applied Photophysics, UK); MCP 300 Polarimeter (Anton Paar, Germany); Fourier Transform Infrared Spectrometer (Shanghai Ruhai Optoelectronic Technology Co., Ltd.); Shimadzu LC-6AD Semi-Preparative Liquid Chromatograph (Beijing Beyond Future Technology Development Co., Ltd.); HB10digital Rotary Evaporator (IKA, Germany); HH-2 Thermostatic Water Bath (Changzhou Guohua Electric Co., Ltd.); DLSBseries Low-Temperature Condensing Circulating Pump (Zhengzhou Great Wall Science & Industry Trade Co., Ltd.); ZF-1 Three-Purpose Ultraviolet Analyzer (Shanghai Jinpeng Analytical Instrument Co., Ltd.); Shumei KQ-500DE Ultrasonic Cleaner (Kunshan Ultrasonic Instrument Co., Ltd.); Cell Culture Incubator NU-5800E (Nuaire, USA); Centrifuge CR412 French company Giant; YXQ-LS-50SⅡ autoclave, Shanghai Boxun Industrial Co., Ltd.; KQ-250E ultrasonic cleaner, Kunshan Ultrasonic Instrument Co., Ltd.; BT-125D electronic analytical balance, Sartorius, Germany; U410-85PRIME ultra-low temperature freezer, NBS, USA; DK-824 electric thermostatic water bath, Shanghai Jinghong Experimental Equipment; Multiskan GO microplate reader, Thermo Fisher Scientific, USA; LEILADMIRB inverted optical microscope, Leica, Germany; NU-543 biosafety cabinet, Nuaire, USA; BD Fortessa flow cytometer, BD, USA.

[0035] 2. Specific methods for extracting and separating compounds include: The extract and water were mixed at a volume ratio of 1 kg: 1 L to obtain a premix. The premix was extracted with an equal volume of n-butanol. The n-butanol phase was then dissolved in 6 times its volume of water to obtain a solution. The solution was first acidified to pH 1 with a 4% hydrochloric acid solution. The solution was then extracted three times with an equal volume of petroleum ether to obtain a petroleum ether extract. The lower acidic solution was adjusted to pH 10 with a 4% sodium hydroxide solution and then extracted three times with an equal volume of chloroform to obtain a total alkaloid extract.

[0036] The total alkaloid extract obtained by chloroform extraction was isocratically eluted by semi-preparative liquid chromatography (methanol: 0.1% trifluoroacetic acid = 60:40, column: ShimNex UP C18 5μm 21.2*250mm, flow rate: 5mL / min). Fractions with the same retention time were combined to obtain four fractions Fr.1~Fr.4. Fr.1 ( t R =12~18min, 8.4g), Fr.2 ( t R =18~25min, 9.5g), Fr.3 ( t R =25~40min, 39.1g), Fr.4 ( t R =40~60min, 59.8g).

[0037] Fr.4 was eluted isocratically with semi-preparative liquid chromatography (methanol: 0.1% trifluoroacetic acid = 55:45, column: ShimNex UP C18 5μm 21.2*250mm; flow rate: 5mL / min). Fractions with the same retention time were combined to obtain four fractions Fr.4-1 to Fr.4-4. Fr.4-1 ( t R =13~25min, 8.8g), Fr.4-2 ( t R =25~35min, 14.8g), Fr.4-3 ( t R =35~48min, 20.6g), Fr.4-4 ( t R =48~65min, 15.1g). Among them, Fr.4-1 was eluted isocratically by semi-preparative liquid chromatography (methanol: 0.1% trifluoroacetic acid = 45:55; column: ShimNex UP C18 5μm 10*250mm; flow rate: 2mL / min) to obtain compound Pactermine Q ( t R =45min, 6.8mg).

[0038] 3. Physicochemical properties of compound Pactermine Q The physicochemical properties of Pactermine Q are as follows: its optical rotation was determined, and its ultraviolet spectrum is as follows. Figure 1 As shown, the infrared spectrum is as follows Figure 2 As shown, nuclear magnetic resonance, including 1 H NMR such as Figure 3 As shown, 13 C NMR such as Figure 4 As shown, DEPT135 Figure 5 As shown, HSQC Figure 6 As shown, 1 H- 1 H COSY as Figure 7 As shown, HMBC is as follows Figure 8 As shown, high-resolution mass spectrometry is as follows Figure 9 As shown.

[0039] Table 1: Compound Pactermine Q 1 H (400MHz) and 13 C (100Hz) NMR data (DMSO- d 6) Note: / indicates no data.

[0040] The physicochemical properties of the alkaloid compound Pactermine Q of this invention are as follows: C 14 H 25 NO3, colorless flaky crystals; α ] 20 D +27.5 ( c 0.05, MeOH); UV (MeOH) λ max <200nm; IR(KBr)ν max :3378, 2955, 2922, 1685, 1198, 1133, 1019, 717cm -1 HR-ESI-MS: m / z 256.1918[M+H] + Single crystals were obtained by culturing in methanol-ethyl acetate, yielding colorless, plate-like crystals with the following crystal structure data: molecular formula C 14 H 25 NO3, copper target (λ=1.54178), Flack parameter=0.12(9), a=7.9904(6)Å, b=23.7315(18)Å, c=7.2171(5)Å, α=90°, β=90°, γ=90°, V=1608.06(7)Å3, single crystal X-ray diffraction results show that the absolute configuration of Pactermine Q is 4S,5S,6S,9S. 1 H-NMR spectrum and 13 C-NMR spectral data are shown in Table 1. UV, IR, NMR, high-resolution mass spectrometry, and single-crystal diffraction results are shown in Table 1. Figures 1-10 .

[0041] 4. Toxicity test against U87 tumor cells U87 cells were preserved in RPMI 1640 medium supplemented with 10% fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin, and cultured at 37°C under 5% CO2 conditions. After cell attachment, the old medium was removed, and trypsin was added to digest the cells. Cell digestion was observed under a microscope. Digestion was stopped when the intercellular spaces increased and the cytoplasm retracted. The digestion solution was aspirated, and the cells were washed with PBS to remove residual liquid. Fresh medium was added, and the cells were transferred to centrifuge tubes for centrifugation. The supernatant was discarded, and fresh medium was added to form a cell suspension. 5.0 × 10⁶ cells were seeded per well in 96-well plates. 4 Cells were cultured for 24 hours. After 24 hours, the antitumor activity of the compounds was measured using the CCK-8 assay. Pactermine Q was dissolved in DMSO, and the culture medium was diluted to final concentrations of 0 μM, 2.5 μM, 5 μM, 10 μM, 25 μM, 50 μM, and 100 μM, with three replicates per group. Temozolomide (TMZ) was used as a positive control, with concentrations of 0 μM, 5 μM, 10 μM, 20 μM, 50 μM, 100 μM, and 200 μM. After culturing for 24, 48, and 72 hours, the old culture medium was removed, and 100 μL of 10% CCK-8 solution was added to each well. The reaction was carried out under the same conditions for 20 minutes, and the absorbance of each well was measured using a microplate reader (450 nm). The IC50 of the drug at different time points was calculated using GraphPad Prism software. 50 (IC) 50 =lg-1[Xm-i(ΣP-0.5)], where Xm is the logarithm of the designed maximum concentration; i is the logarithm of each concentration ratio; ΣP is the sum of growth inhibition rates for each group; and 0.5 is an empirical constant.

[0042] The results showed that, Figure 11 As shown, the compound Pactermine Q has a certain inhibitory effect on U87 cells, with IC50 values ​​at 24h, 48h, and 72h. 50 The IC50 values ​​were 12.3 μM, 5.17 μM, and 3.86 μM, which were superior to the positive control drug TMZ at 24 h, 48 h, and 72 h. 50 The values ​​were 98.12 μM, 74.89 μM, and 58.69 μM.

[0043] 5. Test of apoptosis ability of U87 tumor cells U87 cells were preserved in RPMI 1640 medium containing 10% fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin, and cultured at 37°C under saturated humidity with 5% CO2. When the cells reached the logarithmic growth phase, they were gently digested with PBS containing 0.25% trypsin, collected by centrifugation, and then cultured at 1×10⁻⁶ cells / mL.5 Cells were seeded at a density of 10 cells / well in 24-well plates, with 500 μL of complete culture medium added to each well. The plates were incubated for 24 h to ensure full cell adhesion. After adhesion, the old culture medium was discarded, and pre-prepared drug solutions of different concentrations were added (Pactermine Q diluted to 2.5 μM, 5 μM, and 10 μM with complete culture medium, and TMZ diluted to 10 μM, 50 μM, and 100 μM), with three parallel wells per group. The plates were then incubated at 37°C and 5% CO2 for 48 h. After incubation, the drug solution was discarded, and the cells were gently washed three times with PBS to remove residual drug. Then, a small amount of PBS was added, and the cells were gently detached by pipetting. The cell suspension was transferred to centrifuge tubes and centrifuged at 1000 rpm for 5 min at 4°C. The supernatant was discarded.

[0044] After collecting the cells, take approximately 5 × 10⁶ cells. 4 Cells were resuspended in 195 μL of Annexin V binding buffer, and 5 μL of Annexin V-FITC and 10 μL of propidium iodide (PI) working solution were added sequentially and gently mixed. To ensure staining accuracy, Annexin V-FITC single-staining tubes, PI single-staining tubes, and blank control tubes were also prepared. All samples were incubated at room temperature in the dark for 15 min. After staining, 400 μL of 1× Annexin V binding buffer was added to terminate the reaction. The fluorescence signals of FITC and PI were detected by flow cytometry, and the proportion of apoptotic cells was recorded. The experimental results were analyzed using FlowJo software (v10.6.2) to plot the apoptosis distribution and calculate the apoptosis rate of each group. Finally, the significance of apoptosis rate differences was analyzed using GraphPad Prism software to evaluate the ability of Pactermine Q to induce apoptosis in U87 cells.

[0045] The results showed that, Figure 12 As shown, at 48 h, the compound Pactermine Q had a certain apoptosis-promoting effect on U87 cells. The apoptosis rates of the 2.5 μM, 5 μM and 10 μM Pactermine Q groups were 42.12%, 73.71% and 81.01%, respectively, which were better than the apoptosis rates of 24.27%, 27.71% and 38.98% of the 10 μM, 50 μM and 100 μM positive control drug TMZ groups.

[0046] 6. Investigation of the cell cycle arrest ability of U87 tumor cells U87 cells were preserved in RPMI 1640 medium containing 10% fetal bovine serum, 100 U / mL penicillin, and 100 μg / mL streptomycin, and cultured at 37°C under saturated humidity with 5% CO2. When the cells reached the logarithmic growth phase, they were gently digested with PBS containing 0.25% trypsin, collected by centrifugation, and then incubated at 1×10⁻⁶ cells / mL. 5 Cells were seeded at a density of 1 cell / well in 24-well plates, with 500 μL of complete culture medium added to each well. The plates were incubated for 24 h to ensure full cell adhesion. After adhesion, the old culture medium was discarded, and pre-prepared drug solutions of different concentrations were added (Pactermine Q diluted to 2.5 μM, 5 μM, and 10 μM with complete culture medium, and TMZ diluted to 10 μM, 50 μM, and 100 μM), with three parallel wells per group. The plates were then incubated at 37°C and 5% CO2 for 48 h. After incubation, the drug solution was discarded, and the cells were slowly washed three times with PBS to remove residual drug. Then, a small amount of PBS was added, and the cells were gently detached by pipetting. The cell suspension was transferred to centrifuge tubes and centrifuged at 1000 rpm for 5 min at 4°C. The supernatant was discarded. Approximately 1 mL of pre-chilled PBS was added to resuspend the cells, and the resuspended cells were transferred to 1.5 mL centrifuge tubes. The cells were centrifuged again to precipitate the cell pellet, and the supernatant was carefully aspirated.

[0047] Subsequently, 1 mL of 70% ethanol (pre-chilled on ice) was added, gently mixed by pipetting, and fixed at 4°C for 24 hours. The cells were centrifuged at 1000 rpm for 5 minutes to pellet the cells. Approximately 1 mL of pre-chilled PBS was added to resuspend the cells for washing. The cells were centrifuged again, and the supernatant was carefully aspirated. 500 μL of propidium iodide staining solution was added to each cell sample tube, and the cell pellet was slowly and thoroughly resuspended and incubated at 37°C in the dark for 30 minutes. The cells were then stored on ice in the dark for flow cytometry analysis. The PI signal was detected using a flow cytometer, and light scattering was also measured. Experimental results were analyzed using FlowJo software (v10.6.2) to plot cell cycle distribution and calculate the cell cycle distribution for each group. Finally, GraphPad Prism software was used to analyze the significant differences in cell cycle distribution and evaluate the ability of Pactermine Q to arrest the U87 cell cycle.

[0048] The results showed that, Figure 13As shown, Pactermine Q exhibited a certain cell cycle arrest effect on U87 cells after 48 hours of treatment. Specifically, in the 2.5 μM, 5 μM, and 10 μM Pactermine Q treatment groups, 25.8%, 28.7%, and 35.8% of cells were arrested in S phase, respectively. In contrast, the positive control TMZ, at the corresponding concentrations of 10 μM, 50 μM, and 100 μM, only resulted in 17.5%, 22.4%, and 27.7% of cells being in S phase, respectively. Therefore, Pactermine Q was more effective than the positive control TMZ in promoting S phase arrest in U87 cells.

[0049] It should be noted that when numerical ranges are mentioned in the claims of this invention, it should be understood that the two endpoints of each numerical range and any value between the two endpoints can be selected. To avoid redundancy, the present invention describes preferred embodiments.

[0050] Although preferred embodiments of the invention have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including both the preferred embodiments and all changes and modifications falling within the scope of the invention.

[0051] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A fruit alkaloid called Pactermine Q, characterized in that, The chemical structural formula of the alkaloid Pactermine Q from the fruit of the top-flowered bench is as follows: 。 2. The method for preparing Pactermine Q, an alkaloid from the fruit of the top-flowering vine, as described in claim 1, is characterized in that... Includes the following steps: S1. Extract the fruit of the top flower by reflux with an ethanol solution of 75%~85% by volume, extract 2~4 times, and concentrate the extract to obtain the extract. S2. Mix the extract and water at a volume ratio of 0.5~1.5kg:0.5~1.5L to obtain a premix. Extract the premix with an equal volume of n-butanol. Take the n-butanol phase extract and dissolve it in 5~7 times the volume of water to obtain a solution. Adjust the pH of the solution to 1. Extract the solution 2~4 times with an equal volume of petroleum ether. Then adjust the pH of the solution to 10 and extract it 2~4 times with an equal volume of chloroform to obtain the total alkaloid extract. S3. Elute the total alkaloid extract isocratically with a semi-preparative liquid chromatography system, retaining the fraction Fr.4 with an elution time of 40-60 min. Elute Fr.4 isocratically with a semi-preparative liquid chromatography system, retaining the fraction Fr.4-1 with an elution time of 13-25 min. Elute Fr.4-1 isocratically with a semi-preparative liquid chromatography system, retaining the fraction with an elution time of 40-50 min to obtain Pactermine Q.

3. The use of Pactermine Q, an alkaloid from the fruit of the top flower of claim 1, in the preparation of a drug for treating tumors.

4. The application according to claim 3, characterized in that, The tumors include glioblastoma.

5. The application according to claim 3, characterized in that, The drug is prepared from the alkaloid Pactermine Q of the fruit of the top of the tree and pharmaceutically acceptable excipients.

6. The application according to claim 5, characterized in that, The excipients are selected from any one or more of fillers, stabilizers, diluents, and adjuvants.

7. The application according to claim 6, characterized in that, The diluent is either water or physiological saline.

8. A drug for treating glioblastoma, characterized in that, The drug is composed of Pactermine Q, the alkaloid from the fruit of the fruit of the fruit of claim 1, and excipients, wherein the content of Pactermine Q in the drug is 0.1 wt% to 99 wt%.

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