Beta-carboline derivative as well as preparation method and application thereof

Abstract

The invention relates to the field of natural medicines and medicinal chemistry, in particular to a beta-carboline derivative as well as a preparation method and application thereof, and solves the technical problem of poor activity of existing beta-carboline. The beta-carboline derivative has a structural general formula shown in the specification, wherein R1 is alkyl containing 1-8 carbon atoms; r1 is-OH,-CH3,-OCH3,-F and-N (CH3) 2, and R2 is any one of-OH,-CH3,-OCH3,-F and-N (CH3) 2. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the field of anti-tumor drugs, and in particular to a beta-carboline derivative and a preparation method and application thereof. Background Art

[0002] β-Carboline is a biologically active natural plant-derived alkaloid that has a variety of pharmacological activities, including antispasmodic, antianxiety, antidepressant, anticonvulsant, sedative, analgesic, antimalarial, antiparasitic, etc., and has particularly good anti-tumor activity.

[0003] β-Carboline inhibits tumor cell proliferation and induces apoptosis through three main mechanisms. First, β-Carboline can interact with DNA and change DNA replication; second, it can inhibit cyclin-dependent kinases, topoisomerases, and monoamine oxidases; second, it has an inhibitory effect on benzodiazepines. , 5-HT and other receptors have high affinity.

[0004] However, when the existing β-carboline is directly used for tumor treatment, it has exposed shortcomings: β-carboline is difficult to be absorbed by the body when administered orally, and β-carboline in the plasma will be quickly cleared when injected intravenously. These shortcomings limit the clinical application of β-carboline as a drug, making the existing β-carboline have poor activity and difficult to be directly used in tumor treatment. Summary of the invention

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art, provide a β-carboline derivative and a preparation method and use thereof, and solve the technical problem that the prior β-carboline has poor activity.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] The present invention provides a β-carboline derivative, wherein the β-carboline derivative has a structure as shown in Formula I:

[0008]

[0009] Wherein, R1 is an alkyl group containing 1-8 carbon atoms, and R2 is any one of -OH, -CH3, -OCH3, -F, and -N(CH3)2.

[0010] Optionally, R1 is any one of ethyl, n-propyl, n-butyl and n-pentyl.

[0011] Optionally, the β-carboline derivative has a structure as shown in Formulas I to XII:

[0012]

[0013]

[0014] The present invention provides an application of the above-mentioned β-carboline derivative and a pharmaceutically acceptable salt thereof in the preparation of an anti-tumor drug.

[0015] Optionally, the tumor is a liver cancer tumor, a colorectal cancer tumor or a blood tumor.

[0016] The present invention provides a method for preparing the above-mentioned β-carboline derivative, comprising the following steps:

[0017] L-tryptophan and a benzaldehyde derivative are reacted in the first solvent system to obtain compound 1 through a Pickett-Spengler reaction;

[0018] Compound 1 and thionyl chloride are reacted under a second solvent system through reflux to obtain compound 2;

[0019] Compound 2 is reacted with potassium permanganate in a third solvent system to obtain compound 3;

[0020] Compound 3 and an alkane compound containing two amino groups are subjected to reflux reaction in a fourth solvent system to obtain compound 4;

[0021] Allyl disulfide and 3-mercaptopropionic acid are reacted in a fifth solvent system under a nitrogen atmosphere to obtain compound 5;

[0022] Compound 4 and compound 5 are subjected to an amidation reaction in a sixth solvent system to obtain the β-carboline derivative.

[0023] The synthetic route is as follows:

[0024]

[0025] Among them, the first solvent is 1,2-dichloroethane, the second solvent is anhydrous ethanol, the third solvent is N,N-dimethylformamide, the fourth solvent is methanol, the fifth solvent is diethyl ether and methanol, and the sixth solvent is dichloromethane.

[0026] Optionally, in the step of obtaining the β-carboline derivative by amidation reaction of compound 4 and compound 5 in a sixth solvent system, the mass ratio of compound 4 to compound 5 is 2 to 3:1, and the catalyst is 1-hydroxybenzotriazole and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride.

[0027] Optionally, the molar ratio of the allyl disulfide to the 3-mercaptopropionic acid is 3 to 4:1.

[0028] Optionally, the reaction temperature of the Pickett-Spengler reaction is 100°C to 120°C.

[0029] Compared with the prior art, the present invention uses β-carboline as a lead compound to design and synthesize a class of β-carboline derivatives.

[0030] Pharmacological experiments have shown that the β-carboline derivatives of the present invention have good anti-tumor cell proliferation effects, solving the technical problem of poor activity of existing β-carboline, and the β-carboline derivatives and pharmaceutically acceptable salts thereof can be used to further prepare anti-tumor drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of compound 5 prepared in Example 1 provided by the present invention.

[0032] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 1 provided by the present invention.

[0033] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 2 provided by the present invention.

[0034] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 3 provided by the present invention.

[0035] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 4 provided by the present invention.

[0036] Figure 6 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 5 provided by the present invention.

[0037] Figure 7 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 6 provided by the present invention.

[0038] Figure 8 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 7 provided by the present invention.

[0039] Fig. 9 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 8 provided by the present invention.

[0040] Fig.10 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 9 provided by the present invention.

[0041] Fig.11This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 10 provided by the present invention.

[0042] Fig.12 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 11 provided by the present invention.

[0043] Fig.13 This is the hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 12 provided by the present invention. DETAILED DESCRIPTION

[0044] In order to solve the above technical problems, the present invention provides a β-carboline derivative and a preparation method and use thereof. The technical scheme and embodiments of the present invention are now described in detail in conjunction with the accompanying drawings.

[0045] The present invention is described in detail below through specific examples. The examples are exemplary and intended to be used to explain the present invention, but should not be understood as limiting the present invention.

[0046] Example 1

[0047] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0048] Step 1: Preparation of compound 1.

[0049]

[0050] Using 1,2-dichloroethane as solvent, 24.51mmol of L-tryptophan and 27.00mmol of p-methoxybenzaldehyde were added to the solvent system, 3.75mL of catalyst trifluoroacetic acid was added, and the mixture was heated to 110°C for reaction. After 30 minutes, the reaction was complete as monitored by thin film chromatography, and then the reaction mixture was cooled to room temperature and then poured into a saturated sodium bicarbonate solution. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 4.7g of compound 1.

[0051] Step 2: Preparation of compound 2.

[0052]

[0053] 4.7 g of compound 1 was dissolved in anhydrous methanol, 3.68 mL of thionyl chloride was added dropwise under ice bath conditions, and then refluxed for 6 hours. The reaction was monitored by thin film chromatography. After completion of the reaction, the reaction solution was cooled and concentrated. Then 50 mL of saturated sodium bicarbonate solution was added, extracted with ethyl acetate 3 times, washed with saturated brine once, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 3.5 g of compound 2.

[0054] Step 3: Preparation of compound 3

[0055]

[0056] 3.5 g of compound 2 was dissolved in N,N-dimethylformamide, and 7 g of potassium permanganate was added under ice bath conditions. After reacting for 1 hour, the mixture was transferred to room temperature and reacted for 14 hours. The reaction was monitored by thin film chromatography. The mixture was filtered and the filtrate was dried by spin drying. The mixture was extracted with ethyl acetate 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 2.6 g of compound 3 containing impurities. The mixture was then separated and treated with silica gel column chromatography to obtain 2.0 g of compound 3. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 40:1.

[0057] Step 4: Preparation of compound 4

[0058]

[0059] 2 g of compound 3 was added to 100 mL of methanol, followed by 16 mL of ethylenediamine, and the mixture was heated under reflux for 6 hours. The reaction was monitored by thin film chromatography. When the reaction was complete, the reaction solution was cooled to room temperature, concentrated, and dichloromethane was added. The mixture was washed with water three times, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was separated and treated by silica gel column chromatography to obtain 1.5 g of compound 4. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 20:1.

[0060] Step 5: Preparation of compound 5.

[0061]

[0062] 16.41 mmol of diallyl disulfide was added to a mixed solution containing 10 mL of ether and 20 mL of methanol. Under the protection of nitrogen, 5 mL of ether solution containing 4.62 mmol of 3-mercaptopropionic acid was added, and finally 460 μL of 10N NaOH solution was added to react at room temperature. The reaction was stopped after 24 hours, the reaction solution was concentrated, 30 mL of ether was added, and then washed once with 20 mL of 1M hydrochloric acid solution, and then the organic layer was concentrated. The crude product was separated and treated by silica gel column chromatography to obtain 668 mg of compound 5. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol with a volume ratio of 60:1.

[0063] Step 6: Preparation of β-carboline derivatives.

[0064]

[0065] 46 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 20 mg of compound 5 was added, followed by 16.9 mg of 1-hydroxybenzotriazole and 46.8 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 12 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 106 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula I, with a yield of 48%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0066] Example 2

[0067] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0068] The preparation method is similar to that of Example 1, except that ethylenediamine in step 4 is replaced with propylenediamine, and step 6.

[0069] Step 6: Preparation of β-carboline derivatives.

[0070]

[0071] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula IV, with a yield of 81%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0072] Example 3

[0073] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0074] Refer to the preparation method of Example 2, except that the propylene diamine in step 4 is replaced by butylene diamine, and step 6.

[0075] Step 6: Preparation of β-carboline derivatives.

[0076]

[0077] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula VII, with a yield of 56%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0078] Example 4

[0079] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0080] Refer to the preparation method of Example 2, except that the propylene diamine in step 4 is replaced with pentamethylene diamine, and step 6.

[0081] Step 6: Preparation of β-carboline derivatives.

[0082]

[0083] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula X, with a yield of 68%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0084] Example 5

[0085] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0086] Referring to the preparation method of Example 2, the difference is that the p-methoxybenzaldehyde in step one is replaced by p-fluorobenzaldehyde, the propylenediamine in step four is replaced by ethylenediamine, and step six.

[0087] Step 6: Preparation of β-carboline derivatives.

[0088]

[0089] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then separated and treated by silica gel column chromatography to obtain a β-carboline derivative having a structure of formula II, with a yield of 79%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0090] Example 6

[0091] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0092] Refer to the preparation method of Example 2, except that the p-methoxybenzaldehyde in step one is replaced by p-fluorobenzaldehyde, and step six.

[0093] Step 6: Preparation of β-carboline derivatives.

[0094]

[0095] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula V, with a yield of 41%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0096] Example 7

[0097] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0098] Refer to the preparation method of Example 2, except that the p-methoxybenzaldehyde in step one is replaced by p-fluorobenzaldehyde, the propylenediamine in step four is replaced by butylene diamine, and step six.

[0099] Step 6: Preparation of β-carboline derivatives.

[0100]

[0101] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula VIII, with a yield of 36%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0102] Example 8

[0103] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0104] Refer to the preparation method of Example 2, except that the p-methoxybenzaldehyde in step one is replaced by p-fluorobenzaldehyde, the propylenediamine in step four is replaced by pentamethylenediamine, and step six.

[0105] Step 6: Preparation of β-carboline derivatives.

[0106]

[0107] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula XI, with a yield of 77%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0108] Example 9

[0109] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0110] Refer to the preparation method of Example 2, except that the p-methoxybenzaldehyde in step one is replaced by p-dimethylaminobenzaldehyde, the propylenediamine in step four is replaced by ethylenediamine, and step six.

[0111] Step 6: Preparation of β-carboline derivatives.

[0112]

[0113] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula III, with a yield of 51%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0114] Example 10

[0115] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0116] Refer to the preparation method of Example 2, except that the p-methoxybenzaldehyde in step one is replaced with p-dimethylaminobenzaldehyde, and step six.

[0117] Step 6: Preparation of β-carboline derivatives.

[0118]

[0119] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula VI, with a yield of 52%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0120] Embodiment 11

[0121] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0122] Referring to the preparation method of Example 2, the difference is that the p-methoxybenzaldehyde in step one is replaced by p-dimethylaminobenzaldehyde, the propylenediamine in step four is replaced by butylene diamine, and step six.

[0123] Step 6: Preparation of β-carboline derivatives.

[0124]

[0125] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula IX, with a yield of 51%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0126] Example 12

[0127] This embodiment provides a method for preparing a β-carboline derivative, and the specific steps are as follows:

[0128] Referring to the preparation method of Example 2, the difference is that the p-methoxybenzaldehyde in step one is replaced by p-dimethylaminobenzaldehyde, the propylenediamine in step four is replaced by butylene diamine, and step six.

[0129] Step 6: Preparation of β-carboline derivatives.

[0130]

[0131] 52 mg of compound 4 was dissolved in 5 mL of anhydrous dichloromethane, and then 25 mg of compound 5 was added, followed by 18.9 mg of 1-hydroxybenzotriazole and 53.7 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, stirred at room temperature for 8 hours, monitored by thin film chromatography, and the reaction was complete. Then 10 mL of distilled water was added, extracted with dichloromethane 3 times, washed with saturated brine once, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain 150 mg of crude product. The crude product was then subjected to silica gel column chromatography to obtain a β-carboline derivative having a structure of formula XII, with a yield of 46%. The eluting solvent used in the silica gel column chromatography separation was a mixed solution of dichloromethane and methanol in a volume ratio of 100:1.

[0132] This application was characterized by nuclear magnetic resonance hydrogen spectrum test, and the test results are as follows:

[0133] The hydrogen nuclear magnetic resonance spectrum of compound 5 prepared in Example 1 is as follows: Figure 1 Among them, the δ12.33 (br s, 1H) signal indicates the presence of -COOH substitution in the molecular structure; 5.77-5.87 (m, 1H, -CH=), 5.13-5.23 (m, 2H, =CH2) signals indicate the presence of a terminal double bond in the molecular structure, which proves the successful preparation of compound 5.

[0134] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 1 is as follows: Figure 2Among them, δ9.11 (s, 1H, Ar-NH), 8.80 (s, 1H, H-4), 8.15 (d, J = 7.9 Hz, 1H, Ar-H), 7.55-7.57 (m, 2H, Ar-H), 7.31-7.35 (m, 1H, Ar-H) signals indicate that there is a β-carboline nucleus in the molecular structure; 7.92 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 7.09 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 3.87 (s, 3H, -OCH3) signals indicate that there is a benzene ring substituted with p-methoxy at the 1 position of β-carboline; 8.59 (t, J = 5.7 Hz, 1H, -NH-), 6.83 The signal (t, J=5.2Hz, 1H, -NH-) indicates the presence of two amide groups in the structure; the signals 5.71-5.82 (m, 1H, -CH=), 5.06-5.15 (m, 2H, =CH2) indicate the presence of a terminal double bond in the molecular structure; the signals 3.64-3.68 (m, 2H, -CH2-), 3.49-3.53 (m, 2H, -CH2-), 3.23-3.25 (m, 2H, -CH2-), 2.90-2.93 (m, 2H, -CH2-), 2.57-2.60 (m, 2H, -CH2-) indicate the presence of five methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives having structure of formula I.

[0135] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 2 is as follows: Figure 3Among them, δ9.50 (s, 1H, Ar-NH), 8.79 (s, 1H, H-4), 8.13 (d, J = 7.9 Hz, 1H, Ar-H), 7.57-7.60 (m, 1H, Ar-H), 7.53-7.56 (m, 1H, Ar-H), 7.29-7.33 (m, 1H, Ar-H) signals indicate the presence of a β-carboline nucleus in the molecular structure; 7.92 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 7.06 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 3.84 (s, 3H, -OCH3) signals indicate the presence of a benzene ring substituted with a para-methoxy group at the 1 position of β-carboline; 8.50 (t, J = 6.4 Hz, 1H, -NH-), 7.01 ( The signals of t, J=5.9Hz, 1H, -NH-) indicate that there are two amide groups in the structure; the signals of 5.76-5.86 (m, 1H, -CH=), 5.09-5.18 (m, 2H, =CH2) indicate that there is a terminal double bond in the molecular structure; the signals of 3.55-3.60 (m, 2H, -CH2-), 3.30-3.33 (m, 2H, -CH2-), 3.27-3.29 (m, 2H, -CH2-), 2.92-2.96 (m, 2H, -CH2-), 2.58-2.61 (m, 2H, -CH2-), 1.72-1.78 (m, 2H, -CH2-) indicate that there are six methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives with structure of formula IV.

[0136] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 3 is as follows: Figure 4shown. Among them, δ11.77 (s, 1H, Ar-NH), 8.77 (s, 1H, H-4), 8.38 (d, J = 7.9 Hz, 1H, Ar-H), 7.68-7.70 (m, 1H, Ar-H), 7.56-7.60 (m, 1H, Ar-H), 7.28-7.32 (m, 1H, Ar-H) signals indicate the presence of a β-carboline nucleus in the molecular structure; 8.13 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 7.20 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 3.89 (s, 3H, -OCH3) signals indicate the presence of a benzene ring substituted with a p-methoxy group at the 1-position of β-carboline; 8.67 (t, J = 6.1 Hz, 1H, -NH-), 7.93 (t, J = 5.5 Hz, The signals of 5.74-5.84 (m, 1H, -CH=), 5.09-5.19 (m, 2H, =CH2) indicate the existence of terminal double bonds in the molecular structure; the signals of 3.40-3.43 (m, 2H, -CH2-), 3.35-3.37 (m, 2H, -CH2-), 3.09-3.13 (m, 2H, -CH2-), 2.86-2.90 (m, 2H, -CH2-), 2.44-2.48 (m, 2H, -CH2-), 1.57-1.64 (m, 2H, -CH2-), 1.45-1.52 (m, 2H, -CH2-) indicate the existence of 7 methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives with the structure of formula VII.

[0137] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 4 is as follows: Figure 5shown. Among them, δ9.35 (s, 1H, Ar-NH), 8.82 (s, 1H, H-4), 8.17 (d, J = 7.9 Hz, 1H, Ar-H), 7.56-7.59 (m, 1H, Ar-H), 7.53-7.55 (m, 1H, Ar-H), 7.30-7.34 (m, 1H, Ar-H) signals indicate the presence of a β-carboline nucleus in the molecular structure; 7.92 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 7.08 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 3.84 (s, 3H, -OCH3) signals indicate the presence of a p-methoxy-substituted benzene ring at the 1-position of β-carboline; 8.34 (t, J = 5.6 Hz, 1H, -NH-), 6.08 (t, J = 5.6 Hz, 1 H, -NH-) signals indicate that there are two amide groups in the structure; 5.72-5.82 (m, 1H, -CH=), 5.07-5.15 (m, 2H, =CH2) signals indicate that there is a terminal double bond in the molecular structure; 3.48-3.53 (m, 2H, -CH2-), 3.20-3.25 (m, 4H, -CH2-), 2.89-2.92 (m, 2H, -CH2-), 2.53-2.57 (m, 2H, -CH2-), 1.61-1.68 (m, 2H, -CH2-), 1.53-1.58 (m, 2H, -CH2-), 1.36-1.44 (m, 2H, -CH2-) signals indicate that there are eight methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives having the structure of formula X.

[0138] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 5 is as follows: Figure 6Among them, δ11.85 (s, 1H, Ar-NH), 8.85 (s, 1H, H-4), 8.40 (d, J = 7.9 Hz, 1H, Ar-H), 7.68-7.70 (m, 1H, Ar-H), 7.58-7.62 (m, 1H, Ar-H), 7.29-7.33 (m, 1H, Ar-H) signals indicate that there is a β-carboline nucleus in the molecular structure; 8.25-8.29 (m, 2H, Ar-H), 7.44-7.49 (m, 2H, Ar-H) signals indicate that there is a fluorine-substituted benzene ring at the 1 position of β-carboline; 8.83 (t, J = 5.4 Hz, 1H, -NH-), The signal of 8.17 (t, J = 5.4 Hz, 1H, -NH-) indicates the existence of two amide groups in the structure; the signals of 5.71-5.82 (m, 1H, -CH =), 5.06-5.17 (m, 2H, = CH2) indicate the existence of a terminal double bond in the molecular structure; the signals of 3.46-3.49 (m, 2H, -CH2-), 3.32-3.34 (m, 4H, -CH2-), 2.88-2.91 (m, 2H, -CH2-), 2.48-2.52 (m, 2H, -CH2-) indicate the existence of five methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives having structure of formula II.

[0139] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 6 is as follows: Figure 7 Among them, δ9.23 (s, 1H, Ar-NH), 8.83 (s, 1H, H-4), 8.15 (d, J = 7.9 Hz, 1H, Ar-H), 7.55-7.58 (m, 2H, Ar-H), 7.31-7.35 (m, 1H, Ar-H) signals indicate that there is a β-carboline nucleus in the molecular structure; 7.95-7.99 (m, 2H, Ar-H), 7.24-7.28 (m, 2H, Ar-H) signals indicate that there is a fluorine-substituted benzene ring at the 1 position of β-carboline; 8.45 (t, J = 6.6 Hz, 1H, -NH-), 6.93 (t, J = 6.6 Hz, 1H, -NH- ) signals indicate that there are two amide groups in the structure; 5.77-5.87 (m, 1H, -CH=), 5.10-5.20 (m, 2H, =CH2) signals indicate that there is a terminal double bond in the molecular structure; 3.56-3.61 (m, 2H, -CH2-), 3.28-3.34 (m, 4H, -CH2-), 2.93-2.97 (m, 2H, -CH2-), 2.59-2.63 (m, 2H, -CH2-), 1.74-1.80 (m, 2H, -CH2-) signals indicate that there are six methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives having the structure of formula V.

[0140] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 7 is as follows: Figure 8 Among them, δ11.83 (s, 1H, Ar-NH), 8.81 (s, 1H, H-4), 8.40 (d, J = 7.89 Hz, 1H, Ar-H), 7.68-7.70 (m, 1H, Ar-H), 7.58-7.62 (m, 1H, Ar-H), 7.30-7.33 (m, 1H, Ar-H) signals indicate that there is a β-carboline mother nucleus in the molecular structure; 8.20-8.24 (m, 2H, Ar-H), 7.45-7.49 (m, 2H, Ar-H) signals indicate that there is a fluorine-substituted benzene ring at the 1 position of β-carboline; 8.69 (t, J = 6.1 Hz, 1H, -NH-), 7.92 (t, J = 6.1 Hz, 1H, -NH-) signals indicate that there are 2 The signals of 5.74-5.84 (m, 1H, -CH=), 5.09-5.19 (m, 2H, =CH2) indicated the existence of a terminal double bond in the molecular structure; the signals of 3.39-3.42 (m, 2H, -CH2-), 3.35-3.37 (m, 2H, -CH2-), 3.07-3.12 (m, 2H, -CH2-), 2.86-2.89 (m, 2H, -CH2-), 2.43-2.47 (m, 2H, -CH2-), 1.56-1.63 (m, 2H, -CH2-), 1.44-1.51 (m, 2H, -CH2-) indicated the existence of 7 methylene groups in the structure; the above proton signals proved the successful preparation of β-carboline derivatives having the structure of formula VIII.

[0141] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 8 is as follows: Fig. 9Among them, δ9.57 (s, 1H, Ar-NH), 8.82 (s, 1H, H-4), 8.14 (d, J = 7.9 Hz, 1H, Ar-H), 7.57-7.60 (m, 1H, Ar-H), 7.53-7.55 (m, 1H, Ar-H), 7.29-7.33 (m, 1H, Ar-H) signals indicate the presence of β-carboline nucleus in the molecular structure; 7.94-7 .98 (m, 2H, Ar-H), 7.21-7.25 (m, 2H, Ar-H) signals indicate that there is a fluorine-substituted benzene ring at the 1-position of β-carboline; 8.29 (t, J = 6.1 Hz, 1H, -NH-), 6.11 (t, J = 6.1 Hz, 1H, -NH-) signals indicate that there are two amide groups in the structure; 5.71-5.82 (m, 1H, -CH=), 5.06-5 .15 (m, 2H, = CH2) signal indicates the presence of a terminal double bond in the molecular structure; 3.39-3.42 (m, 2H, -CH2-), 3.35-3.37 (m, 2H, -CH2-), 3.47-3.52 (m, 2H, -CH2-), 3.23-3.25 (m, 2H, -CH2-), 3.19-3.21 (m, 2H, -CH2-), 2.88-2.9 The signals of 1 (m, 2H, -CH2-), 2.53-2.56 (m, 2H, -CH2-), 1.61-1.68 (m, 2H, -CH2-), 1.52-1.58 (m, 2H, -CH2-), 1.36-1.43 (m, 2H, -CH2-) indicated that there were 8 methylene groups in the structure; the above proton signals proved the successful preparation of β-carboline derivatives with structure of formula XI.

[0142] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 9 is as follows: Fig.10Among them, δ9.01 (s, 1H, Ar-NH), 8.78 (s, 1H, H-4), 8.17 (d, J = 7.9 Hz, 1H, Ar-H), 7.54-7.57 (m, 2H, Ar-H), 7.30-7.34 (m, 1H, Ar-H) signals indicate the presence of β-carboline nucleus in the molecular structure; 7.88 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 6.88 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 3.04 (s, 6H, -N(CH3)2) signals indicate the presence of a benzene ring substituted with p-dimethylamino at position 1 of β-carboline; 8.65-8.68 (m, 1H, -NH-), 6. The signals 78-6.81 (m, 1H, -NH-) indicated the presence of two amide groups in the structure; the signals 5.73-5.83 (m, 1H, -CH=), 5.07-5.16 (m, 2H, =CH2) indicated the presence of a terminal double bond in the molecular structure; the signals 3.66-3.70 (m, 2H, -CH2-), 3.51-3.55 (m, 2H, -CH2-), 3.24-3.27 (m, 2H, -CH2-), 2.92-2.97 (m, 2H, -CH2-), 2.58-2.62 (m, 2H, -CH2-) indicated the presence of five methylene groups in the structure; the above proton signals proved the successful preparation of β-carboline derivatives having the structure of Formula III.

[0143] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 10 is as follows: Fig.11Among them, δ9.16 (s, 1H, Ar-NH), 8.78 (s, 1H, H-4), 8.16 (d, J = 7.9 Hz, 1H, Ar-H), 7.55-7.58 (m, 2H, Ar-H), 7.30-7.34 (m, 1H, Ar-H) signals indicate the presence of β-carboline nucleus in the molecular structure; 7.88 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 6.87 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 3.02 (s, 6H, -N(CH3)2) signals indicate the presence of a benzene ring substituted with p-dimethylamino at the 1 position of β-carboline; 8.55 (t, J = 5.8 Hz, 1H, -NH-), 7. The signal of 06 (t, J = 5.8 Hz, 1H, -NH-) indicates the presence of two amide groups in the structure; the signals of 5.78-5.89 (m, 1H, -CH =), 5.11-5.21 (m, 2H, = CH2) indicate the presence of a terminal double bond in the molecular structure; the signals of 3.57-3.62 (m, 2H, -CH2-), 3.30-3.35 (m, 4H, -CH2-), 2.95-2.99 (m, 2H, -CH2-), 2.60-2.64 (m, 2H, -CH2-), 1.74-1.80 (m, 2H, -CH2-) indicate the presence of six methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives having the structure of formula VI.

[0144] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 11 is as follows: Fig.12Among them, δ8.99 (s, 1H, Ar-NH), 8.81 (s, 1H, H-4), 8.18 (d, J = 7.9 Hz, 1H, Ar-H), 7.55-7.57 (m, 2H, Ar-H), 7.30-7.34 (m, 1H, Ar-H) signals indicate that there is a β-carboline nucleus in the molecular structure; 7.87 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 6.89 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 3.04 (s, 6H, -N(CH3)2) signals indicate that there is a benzene ring substituted with p-dimethylamino at the 1 position of β-carboline; 8.45-8.47 (m, 1H, -NH-), 6.28-6.30 (m, 1H, -NH-) signals indicate that There are two amide groups in the structure; 5.76-5.87 (m, 1H, -CH=), 5.10-5.19 (m, 2H, =CH2) signals indicate the presence of a terminal double bond in the molecular structure; 3.53-3.58 (m, 2H, -CH2-), 3.32-3.36 (m, 2H, -CH2-), 3.29-3.31 (m, 2H, -CH2-), 2.94-2.97 (m, 2H, -CH2-), 2.57-2.61 (m, 2H, -CH2-), 1.69-1.74 (m, 2H, -CH2-), 1.62-1.67 (m, 2H, -CH2-) signals indicate the presence of seven methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives having the structure of formula IX.

[0145] The hydrogen nuclear magnetic resonance spectrum of the β-carboline derivative prepared in Example 12 is as follows: Fig.13Among them, δ9.29 (s, 1H, Ar-NH), 8.78 (s, 1H, H-4), 8.17 (d, J = 7.9 Hz, 1H, Ar-H), 7.55-7.58 (m, 1H, Ar-H), 7.51-7.53 (m, 1H, Ar-H), 7.29-7.32 (m, 1H, Ar-H) signals indicate that there is a β-carboline core in the molecular structure. ; 7.88 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 6.84 (dd, J = 8.8, 2.0 Hz, 2H, Ar-H), 2.98 (s, 6H, -N(CH3)2) signals indicate the presence of a benzene ring substituted with p-dimethylamino at the 1-position of β-carboline; 8.41 (t, J = 6.5 Hz, 1H, -NH-), 6.12 (t, J = 6.5 Hz ,1H,-NH-) signals indicate that there are two amide groups in the structure; 5.72-5.83 (m,1H,-CH=), 5.07-5.15 (m,2H,=CH2) signals indicate that there is a terminal double bond in the molecular structure; 3.48-3.53 (m,2H,-CH2-), 3.20-3.25 (m,4H,-CH2-), 2.89-2.93 (m,2H,-CH2-), 2.53-2.57 (m,2H,-CH2-), 1.63-1.68 (m,2H,-CH2-), 1.53-1.58 (m,2H,-CH2-), 1.37-1.44 (m,2H,-CH2-) signals indicate that there are eight methylene groups in the structure; the above proton signals prove the successful preparation of β-carboline derivatives with the structure of formula XII.

[0146] The following are the pharmacological experiments of some compounds of the present invention:

[0147] Instruments used in the experiment: clean bench, manufactured by Sujing Group Antai Company. Constant temperature incubator, manufactured by Thermo Electron Corporation. Microplate reader, manufactured by BIO-RAD Company. Inverted biological microscope, manufactured by Chongqing Optical Instrument Factory.

[0148] Reagents used in the experiment: cell culture medium RPMI-1640 and high-glucose DMEM, manufactured by GIBCO. Fetal bovine serum, manufactured by Hangzhou Sijiqing Co., Ltd. CCK-8, manufactured by Biosharp. DMSO, manufactured by Sigma.

[0149] Cell lines used in the experiment: human myeloid leukemia cells HL-60, human histiocytic lymphoma leukemia cells U937, human hepatoma cells HepG2, human colorectal cancer cells HCT-116

[0150] The cytotoxic activity test method is as follows:

[0151] (1) The cytotoxic activity of these compounds against tumor cells HL-60 and U937 was tested by trypan blue staining. HL-60 and U937 cells in the logarithmic growth phase were taken and 5×10 4 The cells were inoculated at a concentration of 100 μg / mL in a 24-well plate, 2 mL of cell suspension was added to each well, and then the corresponding concentration of drug-containing culture medium was added. A blank control group and a positive control group were set up at the same time, and then the 24-well plate was placed in an incubator at 37°C and 5% CO2 for culture. After 72 hours, 50 μL of cell suspension was aspirated into each well, and then 50 μL of 0.4% trypan blue solution was added. After mixing, 10 μL was aspirated into a blood cell counting plate, and the total number of cells in the control group and the drug-dosed group were counted under a microscope. The growth inhibition rate of the compound at this concentration is calculated as the percentage of the total number of cells in each well to the total number of cells in the control well. Finally, SPSS software was used to calculate the IC by the probability unit weighted regression method. 50 value.

[0152] (2) The effects of these compounds on the proliferation of HepG2 and HCT-116 cells were evaluated in vitro using the CCK-8 method. HepG2 and HCT-116 cells in the logarithmic growth phase were selected, digested, counted, and prepared into a concentration of 5×10 4 100 μL of cell suspension was added to each well of a 96-well cell culture plate; the 96-well cell culture plate was then placed in an incubator at 37°C and 5% CO2 for 24 hours, and then 100 μL of drug-containing culture medium was added to each well, and then placed in an incubator for culturing. After 72 hours, the 96-well plate was stained with CCK-8, and 10 μL of CCK-8 was added to each well, and the plate was further cultured in the incubator for 3 hours, and then placed on a shaker and gently mixed for 10 minutes, and then the absorbance value at a wavelength of 450 nm was measured with an enzyme marker, and the inhibition rate was calculated. The calculation formula is inhibition rate (%) = 100-[(A 加药 -A 空白 ) / (A 0加药 -A 空白 )]×100%. Finally, SPSS software was used to calculate IC by probability unit weighted regression method. 50 value.

[0153] IC 50 Refers to the half inhibitory concentration. Tumor cells were cultured with the test compound for 72 hours, and the IC was determined by trypan blue staining or CCK-8 assay. 50 All data are expressed as the mean ± standard deviation of three independent experiments. The experimental results are shown in Table 1.

[0154] Table 1 IC of the antiproliferative activity of the examples against four cancer cell lines50 Value (μM)

[0155] sample HL-60 U937 HepG2 HCT-116 Example 1 2.98±0.13 4.63±0.29 20.27±0.81 10.37±0.62 Example 2 3.91±0.22 6.93±0.34 12.28±0.76 4.08±0.25 Example 3 5.42±0.37 5.53±0.22 >50 81.44±3.96 Example 4 4.61±0.16 5.61±0.38 >50 >100 Example 5 4.37±0.25 5.97±0.15 22.69±0.93 9.61±0.58 Example 6 4.67±0.11 6.59±0.23 11.88±0.69 2.84±0.21 Example 7 28.01±1.18 7.33±0.17 42.55±2.93 18.43±0.85 Example 8 5.24±0.27 6.92±0.19 >50 17.25±1.06 Example 9 1.99±0.09 3.18±0.13 26.93±1.23 9.06±0.03 Example 10 7.23±0.21 7.98±0.62 >50 >100 Embodiment 11 13.58±0.67 16.73±1.31 >50 >100 Example 12 15.86±0.45 6.68±0.11 >50 >100 Compound 5 36.30±1.09 >50 >50 >100 harmine 7.05±0.34 8.11±0.25 16.97±1.02 13.90±0.31 5-FU 2.59±0.21 0.95±0.07 32.70±2.14 12.19±0.13

[0156] Among them, the full name of 5-FU is 5-Fluorouracil, and its Chinese name is fluorouracil. Harmine is a β-carboline alkaloid with a chemical formula of C 11 H 12 N2O, whose Chinese name is harmaline.

[0157] Pharmacological experiments have shown that the β-carboline derivatives of the present invention have better anti-proliferation activity against liver cancer tumors, colorectal cancer tumors and blood tumor cells, solving the technical problem of poor activity of existing β-carboline. The β-carboline derivatives and pharmaceutically acceptable salts thereof can be used to further prepare anti-tumor drugs.

[0158] The above description is only a preferred embodiment of the present invention, and the above specific embodiment is not intended to limit the present invention. Various deformations and modifications may occur within the scope of the technical concept of the present invention, and any modification, modification or equivalent replacement made by a person of ordinary skill in the art based on the above description shall fall within the scope of protection of the present invention.

Claims

1. A β-carboline derivative, characterized in that: The β-carboline derivative has the following general structural formula: Wherein, R1 is an alkyl group containing 1-8 carbon atoms; R2 is any one of -OH, -CH3, -OCH3, -F and -N(CH3)2.

2. The β-carboline derivative according to claim 1, characterized in that R1 is any one of ethyl, n-propyl, n-butyl and n-pentyl.

3. The β-carboline derivative according to claim 2, characterized in that The β-carboline derivatives have structures as shown in Formulas I to XII:

4. Use of the β-carboline derivative and a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3 in the preparation of anti-tumor drugs.

5. The use of the β-carboline derivative and the pharmaceutically acceptable salt thereof in the preparation of anti-tumor drugs according to claim 4, characterized in that: The tumor is a liver cancer tumor, a colorectal cancer tumor or a blood tumor.

6. A method for preparing the β-carboline derivative according to any one of claims 1 to 3, characterized in that: The steps include: L-tryptophan and a benzaldehyde derivative are reacted in the first solvent system to obtain compound 1 through a Pickett-Spengler reaction; Compound 1 and thionyl chloride are reacted under a second solvent system through reflux to obtain compound 2; Compound 2 is reacted with potassium permanganate in a third solvent system to obtain compound 3; Compound 3 and an alkane compound containing two amino groups are subjected to reflux reaction in a fourth solvent system to obtain compound 4; Allyl disulfide and 3-mercaptopropionic acid are reacted in a fifth solvent system under a nitrogen atmosphere to obtain compound 5; Compound 4 and compound 5 are subjected to an amidation reaction in a sixth solvent system to obtain the β-carboline derivative; 7. The method for preparing a β-carboline derivative according to claim 6, characterized in that: In the step of obtaining the β-carboline derivative by amidation reaction of compound 4 and compound 5 in a sixth solvent system, the mass ratio of compound 4 to compound 5 is 2 to 3:1, and the catalyst is 1-hydroxybenzotriazole and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride.

8. The method for preparing a β-carboline derivative according to claim 6, characterized in that: The fifth solvent is diethyl ether and methanol, and the molar ratio of the allyl disulfide to the 3-mercaptopropionic acid is 3-4:

1.

9. The method for preparing a β-carboline derivative according to claim 6, characterized in that: The first solvent is 1,2-dichloroethane, and the reaction temperature of the Pickett-Spengler reaction is 100° C. to 120° C.

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