Compound with anti-tumor activity and preparation method and application thereof

Abstract

The present invention discloses a compound with anti-tumor activity, which has the following structural formula: The present invention also provides a method for preparing a compound with anti-tumor activity, wherein the carboxyl group on the first amino acid at the C-terminus of the CS-piscidin polypeptide is connected to the amino group of the side chain of the Cyclo-RGDfk polypeptide to obtain the CS-RGD polypeptide; the amino group on the first amino acid at the N-terminus of the CS-RGD polypeptide is connected to the carboxyl group on myristic acid to obtain the Myr-CS polypeptide. The present invention also provides the use of a compound with anti-tumor activity in the preparation of an anti-tumor drug. The Myr-CS polypeptide of the present invention has stronger targeting to cancer cells such as leukemia cells and ovarian cancer cells, exhibits good anti-tumor effects, has low toxicity to normal cells, and has higher drug safety.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology. More specifically, the present invention relates to a compound with anti-tumor activity and a preparation method and application thereof. Background Art

[0002] Malignant tumors, whether solid or non-solid, have the characteristics of rapid development, poor prognosis, and uncontrolled growth, which seriously endangers human health. Current conventional cancer-centered therapies are not enough to eradicate malignant tumors. In addition, the tolerance of malignant tumors to conventional therapies further increases the difficulty of treatment and the possibility of recurrence. Therefore, the treatment of malignant tumors faces a huge challenge, that is, how to increase tumor cell targeting and reduce damage to normal cells or tissues while eliminating malignant tumors.

[0003] Leukemia is a type of gene mutation disease with complex classification. Compared with solid tumors, leukemia has innate unique abilities in migration and invasion. Therefore, the treatment of leukemia is usually challenging. Currently, most clinical treatments for leukemia are chemotherapy and bone marrow hematopoietic stem cell transplantation. The site of action of radiotherapy is unclear and the systemic side effects are large, while bone marrow hematopoietic stem cell transplantation is limited by issues such as bone marrow source, cost, and age. Therefore, chemotherapy using chemotherapy drugs such as alkylating agents, anthracyclines, and alkaloids is the current conventional treatment for leukemia. However, existing chemotherapy drugs have low selectivity. While clearing cancer cells, they are also toxic to normal hematopoietic stem cells and vascular epithelial cells. The adverse reactions to the blood system caused by them limit the use of chemotherapy drugs. Therefore, there is an urgent need to develop new chemotherapy drugs for the treatment of leukemia.

[0004] Ovarian cancer is the third most common gynecological malignancy in the world. According to statistics, more than 125,000 women die of ovarian cancer each year worldwide. Studies have shown that this number is still rising and is expected to exceed 250,000 by 2035. Due to the lack of non-specific symptoms and effective screening methods, ovarian cancer is generally "hidden" and is not diagnosed until symptoms appear in the late stage, when it has already metastasized to other tissues, increasing the difficulty of treatment. In addition, ovarian cancer has obvious tumor heterogeneity. Different etiologies, molecular biological characteristics, and many other characteristics make it impossible to eliminate all ovarian cancer cells with a single drug. At present, chemotherapy with platinum or paclitaxel drugs after tumor cell reduction surgery is still the preferred treatment method. However, adverse reactions such as nephrotoxicity, hematotoxicity, ototoxicity, hepatotoxicity, gastrointestinal toxicity, and neurotoxicity caused by platinum, as well as the repeated emergence of drug resistance, limit the application of drugs. Therefore, it is of great clinical significance to develop highly effective and low-toxic anti-ovarian drugs to effectively treat and prevent the recurrence and metastasis of ovarian cancer.

[0005] Antimicrobial peptides are antimicrobial peptides that are widely found in many types of organisms. They are one of the natural immune defense barriers of organisms. In addition to antimicrobial function, recent studies have found that they also have anti-tumor activity. In addition, due to the low cost of peptide synthesis, easy modification, high activity, non-toxic metabolites, and easy to overcome drug resistance, they have recently become a research hotspot in the field of anti-tumor.

[0006] At present, anticancer peptides have been preliminarily studied, developed and utilized, such as anti-lung cancer peptides, peptides with broad-spectrum anticancer effects such as LXP-7, and peptides that can inhibit cancer cell migration and invasion, but there are few patents for peptides for the treatment of leukemia and ovarian cancer, and there is a lack of systematic evaluation. For example, CN106029683B-A polypeptide and polypeptide complex for inhibiting tumor metastasis and treating leukemia, its preparation method and its application discloses two polypeptide sequences, which confirm that the polypeptide has the effects of inhibiting cell migration and promoting apoptosis on leukemia cells at the same time, and can achieve the effect of inhibiting 50% cell migration at 1μM, but even if the concentration reaches 80μM, it can only induce apoptosis in 25% of cells. If the drug dosage is further increased, the safety of the drug cannot be guaranteed.

[0007] CN111848737A-A small molecule polypeptide drug and its application in the treatment of acute myeloid leukemia discloses that both the left-handed and right-handed isomers of a polypeptide can achieve anti-leukemia effects by inducing THP-1 differentiation, but the patent only tests one leukemia cell line, and it is still necessary to conduct anti-tumor evaluation and normal cell toxicity evaluation in multiple leukemia cell lines. CN112457384A-An enzymatic polypeptide and its use in the preparation of anti-leukemia drugs also do not conduct multi-cell evaluation of the polypeptide. CN112979753A, CN112225821A-provide a variety of polypeptide sequences with broad-spectrum anti-cancer effects, proving that the polypeptide has the effect of inhibiting cell proliferation and invasion on multiple cancer cells including ovarian cancer cell SKOV3, but the patent only tests one ovarian cancer cell line, and it is still necessary to conduct anti-tumor and normal cell toxicity evaluation in multiple ovarian cancer cells, and there is still a lack of in vivo anti-tumor activity detection data of the polypeptide. CN114369171A-A chimeric antigen receptor fused with a polypeptide and an antibody, the in vivo anti-tumor activity of the complex was detected in subcutaneous ovarian cancer-bearing mice, but the subcutaneous tumor model does not conform to the actual incidence of ovarian cancer in patients, and further testing of its anti-tumor activity using abdominal tumor-bearing mice is still required. CN114222580A-Provides a polypeptide sequence with the function of clearing in situ ovarian cancer in mice, but the patent only evaluates the activity in vivo, and has not yet evaluated the toxicity to normal ovarian cells. Therefore, the development of new polypeptide drugs is of great significance for the clinical screening of anti-tumor drugs. Summary of the invention

[0008] An object of the present invention is to solve at least the above problems and to provide at least the advantages which will be described hereinafter.

[0009] One object of the present invention is to provide a compound with anti-tumor activity, which has good inhibitory activity on the growth of tumor cells.

[0010] In order to achieve these purposes and other advantages of the present invention, a compound Myr-CS polypeptide having anti-tumor activity is provided, which has the following structural formula:

[0011]

[0012] The preparation method of the compound with anti-tumor activity comprises connecting the carboxyl group on the first amino acid at the C-terminus of the CS-piscidin polypeptide with the amino group on the side chain of the Cyclo-RGDfk polypeptide to obtain the CS-RGD polypeptide; and connecting the amino group on the first amino acid at the N-terminus of the CS-RGD polypeptide with the carboxyl group on myristic acid to obtain the Myr-CS polypeptide.

[0013] A method for preparing a compound with anti-tumor activity and its application in preparing anti-leukemia drugs and anti-ovarian cancer drugs.

[0014] The present invention has at least the following beneficial effects:

[0015] First, the present invention uses the modified CS-RGD polypeptide and Myr-CS polypeptide to treat leukemia cells K562, THP-1, JURKAT and U937. The results show that compared with the CS-piscidin polypeptide, the CS-RGD polypeptide and the Myr-CS polypeptide significantly enhance the killing of leukemia cells and exhibit good anti-tumor effects. In addition, the minimum effective concentration of the Myr-CS polypeptide is significantly lower than the minimum toxic concentration of normal venous epithelial cells, with a large therapeutic window and higher drug safety.

[0016] Second, after the CS-piscidin polypeptide is modified by Cyclo-RGDfk and myristic acid, the anti-cancer activity of the target Myr-CS polypeptide obtained by the present invention is further improved, and the effect of eliminating 50% of leukemia cells can be achieved under the condition of 3 to 8 times lower than the minimum toxic concentration of normal venous epithelial cells.

[0017] Third, the present invention uses the modified CS-RGD polypeptide and Myr-CS polypeptide to treat normal ovarian epithelial cells IOSE80. The results show that compared with the CS-piscidin polypeptide, the Myr-CS polypeptide significantly reduces the killing effect on normal ovarian epithelial cells, has stronger targeting and higher safety.

[0018] Fourth, the present invention uses the original polypeptide CS-piscidin and the modified CS-RGD polypeptide and Myr-CS polypeptide to treat the in vivo model of ovarian cancer-bearing mice. The results show that compared with the CS-piscidin polypeptide, the Myr-CS polypeptide significantly enhances the in vivo cancer cell clearance effect on tumor-bearing mice and has a better in vivo therapeutic effect.

[0019] Other advantages, objectives and features of the present invention will be embodied in part through the following description, and in part will be understood by those skilled in the art through study and practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a graph comparing the inhibition of CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide on different leukemia cells;

[0021] Figure 2 This is a graph comparing the inhibitory effects of CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide on the growth of venous epithelial cells;

[0022] Figure 3 This is a graph comparing the inhibition of the growth activity of different ovarian cancer cells by CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide;

[0023] Figure 4 This is a graph comparing the inhibition of normal ovarian epithelial cell growth activity by CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide;

[0024] Figure 5a This is a result of Image J analysis of the micrographs of the test of inhibition of spheroid formation of different ovarian cancer cells by CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide;

[0025] Figure 5b This is a diagram showing the results of cell clone data analysis of the spherical cyst formation inhibition test of CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide on different ovarian cancer cells;

[0026] Figure 6 This is a flow cytometry result diagram comparing the induction of death of different ovarian cancer cells by CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide;

[0027] Figure 7 This is a diagram comparing the therapeutic effects of CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide on tumor-bearing mice. DETAILED DESCRIPTION

[0028] The present invention is further described in detail below in conjunction with the accompanying drawings so that those skilled in the art can implement the invention with reference to the description.

[0029] It should be understood that the terms such as “having”, “including” and “comprising” used herein do not exclude the existence or addition of one or more other elements or combinations thereof.

[0030] It should be noted that the experimental methods described in the following embodiments are conventional methods unless otherwise specified, and the reagents and materials can be obtained from commercial channels unless otherwise specified.

[0031] The amino acid sequence of the CS-piscidin polypeptide of the present invention is FFKRLRNKFRLMRQAWKDYR; the structural formula is:

[0032]

[0033] The structural formula of myristic acid of the present invention is:

[0034]

[0035] The structural formula of the Cyclo-RGDfk polypeptide of the present invention is:

[0036]

[0037] A method for preparing a compound with anti-tumor activity comprises connecting the carboxyl group on the first amino acid at the C-terminus of a CS-piscidin polypeptide with the amino group on the side chain of a Cyclo-RGDfk polypeptide to obtain a CS-RGD polypeptide; and connecting the amino group on the first amino acid at the N-terminus of a CS-RGD polypeptide with the carboxyl group on myristic acid to obtain a Myr-CS polypeptide.

[0038] The order of modifying the CS-piscidin polypeptide with Cyclo-RGDfk polypeptide or myristic acid is not a limitation to the protection scope of the present invention. For example, in some embodiments, the CS-piscidin polypeptide can be modified with myristic acid first, and then the CS-piscidin polypeptide modification product of myristic acid can be modified with Cyclo-RGDfk polypeptide; or the CS-piscidin polypeptide can be modified with myristic acid and Cyclo-RGDfk polypeptide at the same time, which are all within the protection scope of the present invention.

[0039] Myr-CS polypeptide has the following structural formula:

[0040]

[0041] <Effect Test>

[0042] 1. Toxicity detection of CS-piscidin, Myr-CS and CS-RGD on different leukemia cell lines

[0043] Myeloid leukemia cells K562, monocytic leukemia cells THP-1, lymphoid leukemia cells JURKAT and myeloid leukemia cells U937 were used as model systems for studying leukemia cell lines. All cell lines were cultured in RPMI-1640 medium (containing a mixed solution of 10% fetal bovine serum FBS and 1% penicillin-streptomycin) at 37°C in an incubator with 5% CO2.

[0044] Unless otherwise specified, the culture maintenance conditions mentioned below are all RPMI-1640 medium (containing a mixed solution of 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin) and 37°C and 5% CO2.

[0045] In a 96-well plate, add 90 μL of 2 × 10 3 After the culture medium of each cell was added, 10 μL of culture medium solution of different concentrations of polypeptide was added to each well of the culture plate, so that the final concentration of the polypeptide was 1 μM, 5 μM, and 10 μM. The blank control group was added with 10 μL of culture medium solution, and the background control well was 100 μL of culture medium solution. The culture plate was placed in the incubator for 48 h or 72 h, and 10 μL of CCK-8 solution (Shanghai Biyuntian Biotechnology Co., Ltd.) was added to each well. After the culture plate was placed in the incubator for 2 h, the absorbance value (OD value) at a wavelength of 450 nm was measured with a multifunctional microplate reader, and the cell viability was calculated using the following formula:

[0046] Cell viability = (OD 多肽 -OD 背景 ) / (OD 空白对照组 -OD 背景 )×100%.

[0047] All data were analyzed and counted using Graphpad prism. Cell viability analysis results are shown in Figure 1 The IC50 analysis results are shown in Table 1.

[0048] Table 1 The half inhibitory concentration (IC50) of each peptide on the activity of leukemia cells from different sources

[0049]

[0050]

[0051] Figure 1As shown in the results of Table 1, Myr-CS, CS-RGD polypeptide and CS-piscidin have different inhibitory effects on leukemia cells from different sources; Myr-CS and CS-RGD polypeptides have more significant inhibitory effects on the four leukemia cells compared with CS-piscidin. It can be seen that CS-piscidin has the effect of enhancing the killing ability of leukocytes after being modified with Cyclo-RGDfk polypeptide, or modified with Cyclo-RGDfk polypeptide and myristic acid.

[0052] 2. Comparison of the inhibitory effects of CS-piscidin, Myr-CS and CS-RGD on the cell viability of HUVEC cells

[0053] In a 96-well plate, add 100 μL of 2 × 10 3 The culture medium of each cell was placed in a cell culture incubator for culture. After the cells were completely attached to the wall, the old culture medium was discarded, and 100 μL of culture medium solution with different concentrations of polypeptides was added to each well of the culture plate, where the concentrations of the polypeptides were 1 μM, 3 μM, 10 μM, 30 μM, and 50 μM. The blank control group was only added with 100 μL of culture medium solution, and the background control well was 100 μL of culture medium solution. After the culture plate was placed in the incubator for 24 hours, 10 μL of CCK-8 solution (Shanghai Biyuntian Biotechnology Co., Ltd.) was added to each well. After the culture plate was placed in the incubator for 2 hours, the absorbance value (OD value) at a wavelength of 450 nm was measured with a multifunctional microplate reader, and the cell survival rate was calculated using the following formula:

[0054] Relative cell viability = (OD 多肽 -OD 背景 ) / (OD 空白对照组 -OD 背景 )×100%.

[0055] All data were analyzed and counted using Graphpad prism. The results of relative cell survival rate analysis are shown in Figure 2 The IC50 analysis results are shown in Table 2 below.

[0056] Table 2 The half inhibitory concentration (IC50) of each peptide on the activity of human venous epithelial cells

[0057] CS-piscidin CS-RGD Myr-CS HUVEC 40.850μM 9.177μM 83.360μM

[0058] From the results in Table 2, it can be seen that CS-RGD has a strong inhibitory effect on the viability of human venous epithelial cells. Modification of CS-RGD peptide with myristic acid can not only enhance the anti-leukemia effect but also reduce the toxicity to normal venous epithelial cells, providing a selective modification scheme for the use of peptides to treat multi-lineage leukemia.

[0059] 3. Short-term inhibition test of CS-piscidin peptide, Myr-CS peptide and CS-RGD peptide on the growth activity of different ovarian cancer cells

[0060] Human ovarian cancer cells OVCA429, A2780 and SKOV3 and mouse ovarian cancer ID8 were used as model systems for studying ovarian cancer cell lines. All cell lines were cultured in DMEM medium (containing 10% fetal bovine serum FBS and 1% penicillin-streptomycin mixed solution) at 37°C and 5% CO2 in an incubator.

[0061] Unless otherwise specified, the culture maintenance conditions mentioned below are all DMEM medium (containing a mixed solution of 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin) and 37°C and 5% CO2.

[0062] In a 96-well plate, add 100 μL of 2 × 10 3 After the culture plate is incubated with the culture medium of each cell, it is placed in a cell culture incubator for culture. After the cells are completely attached to the wall, the old culture medium is discarded, and 100 μL of culture medium solution with different concentrations of polypeptides is added to each well of the culture plate, where the concentrations of the polypeptides are 1 μM, 3 μM, 10 μM, 20 μM, and 30 μM. The blank control group is only added with 100 μL of culture medium solution, and the background control well is 100 μL of culture medium solution. After the culture plate is in the incubator for 24 hours, 10 μL of CCK-8 solution (Shanghai Biyuntian Biotechnology Co., Ltd.) is added to each well. After the culture plate is in the incubator for 2 hours, the absorbance value (OD value) at a wavelength of 450 nm is measured with a multifunctional microplate reader, and the cell survival rate is calculated using the following formula:

[0063] Relative cell viability = (OD 多肽 -OD 背景 ) / (OD 空白对照组 -OD 背景 )×100%.

[0064] All data were analyzed and counted using Graphpad prism. Cell viability analysis results are shown in Figure 3 The IC50 analysis results are shown in Table 3.

[0065] Table 3 The half inhibitory concentration (IC50) of each peptide on the activity of different ovarian cancer cells

[0066] OVCA429 A2708 SKOV3 ID8 CS-piscidin 8.588μM 17.73μM 40.38μM 14.65μM CS-RGD 6.257μM 10.56μM 19.71μM 9.142μM Myr-CS 14.40μM 25.80μM 34.10μM 24.66μM

[0067] Figure 3As shown in the results of Table 3, Myr-CS, CS-RGD peptide and CS-piscidin have different inhibitory effects on different ovarian cancer cells; CS-RGD peptide has a more significant inhibitory effect on four ovarian cancer cells compared with CS-piscidin; Myr-CS has a weakened short-term inhibitory effect on three ovarian cancer cells except SKOV3.

[0068] IV. Long-term inhibition test of the growth activity of normal human ovarian epithelial cells by CS-piscidin peptide, Myr-CS peptide and CS-RGD peptide

[0069] The method for comparing the long-term inhibitory effects of CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide on the growth activity of normal human ovarian epithelial cells is the same as step 3. The results of cell viability analysis are as follows Figure 4 The IC50 analysis results are shown in Table 4.

[0070] Table 4 The half inhibitory concentration (IC50) of each peptide on the activity of normal human ovarian epithelial cells

[0071] CS-piscidin CS-RGD Myr-CS IOSE80 15.15μM 7.466μM 31.79μM

[0072] from Figure 4 As shown in the results of Table 4, CS-RGD has a strong inhibitory effect on the viability of normal human ovarian epithelial cells. After the CS-RGD peptide is modified with myristic acid, its toxicity to normal epithelial cells is reduced and its safety is higher, which provides a selective modification scheme for the use of peptides in the adjuvant treatment of ovary.

[0073] 5. Inhibition test of spheroid formation by CS-piscidin peptide, Myr-CS peptide and CS-RGD peptide on different ovarian cancer cells

[0074] Mouse ovarian cancer cell ID8 and human ovarian cancer cell OVCA429 were used as model systems for studying ovarian cancer cell lines. 1 mL of 1×10 3After the culture medium of each cell was added, 0.5 mL of culture medium solution containing different polypeptide concentrations was added to each well of the culture plate to make the final concentrations of 3 μM and 10 μM. The blank control group was 0.5 mL of culture medium solution without polypeptide. After 5 days of drug action, the cell suspension was gently transferred into an ordinary six-well plate to allow it to adhere to the wall. After adhesion, the culture medium was replaced every 2-3 days. After the formation of cell clones of effective size (cell number ≥ 50), the cells were rinsed twice with PBS and fixed with paraformaldehyde at room temperature for 20 minutes, rinsed twice with PBS, incubated with 0.1% crystal violet at room temperature for 20 minutes, washed with PBS and dried, and photographed under a microscope. The images were analyzed and processed with Image J. The data obtained were analyzed and statistically analyzed using Graphpadprism. The results of cell clone data analysis are shown in the figure below. Figure 5a , 5b shown.

[0075] Figure 5a , 5b The results showed that ovarian cancer cells exposed to Myr-CS for a long time were still sensitive to the tested peptide.

[0076] 6. Flow cytometry study of the induction of death of different ovarian cancer cells by CS-piscidin peptide, Myr-CS peptide, and CS-RGD peptide

[0077] SKOV3, ID8, and OVCA429 cells were evenly inoculated into 6-well plates and cultured in an incubator. After the cells were completely attached to the wall, the old culture medium was discarded and 1.5 mL of culture medium solution containing the specified polypeptide concentration was added to each well of the culture plate. The blank control group was 1.5 mL of culture medium solution. After 24 hours of polypeptide action, the cells were washed twice with PBS and digested with trypsin cell digestion solution (EDTA-free, Bio-Time, C0205). The digestion was terminated with DMEM, and the cells were collected by centrifugation and washed twice with PBS. The cells were stained and tested on the machine according to the Annexin V-FITC / PI double-staining cell apoptosis detection kit (BL107A, biosharp). The flow cytometry results are shown in the figure. Figure 6 shown.

[0078] Figure 6 The results showed that compared with CS-piscidin peptide, CS-RGD peptide could induce more cells to enter apoptosis, especially late apoptosis, while the ability of Myr-CS modified with myristic acid to induce cell death was weakened.

[0079] VII. Experiment on the therapeutic effect of CS-piscidin peptide, Myr-CS peptide and CS-RGD peptide on tumor-bearing mice

[0080] Four-week-old C57BL / 6 mice were purchased from Yancheng Biological Company. The mice were housed in specific pathogen-free, temperature- and humidity-controlled, independently ventilated IVC cages. All mice were allowed to adapt to the environment for one week before the experiment began. The plasmid encoding the firefly luciferase reporter gene was transduced into mouse ovarian cancer cell ID8 using a lentiviral packaging vector, and 1 μg / ml puromycin was used for selection to obtain Luc-ID8 cells that can stably express and stably passage. The cells were then cultured according to the Bio-Lumi TM II Firefly Luciferase Reporter Gene Assay Kit Instructions Lyse cells (Biyuntian, RG043S) and use a multifunctional microplate reader (MithrasLB940) to detect the in vitro expression of luciferase. After successfully constructing cells expressing the luciferase reporter gene, 5 million Luc-ID8 cells were resuspended in 200 μL PBS and injected intraperitoneally into mice. One week later, CS-piscidin, Myr-CS and CS-RGD polypeptides were injected intraperitoneally into mice at a dose of 2.5 mpk, once every two days, for 10 consecutive times. After the last injection, the animal in vivo imaging system was used to detect the fluorescence distribution in the mouse (In-Vivo Xtreme), and the images were statistically analyzed using Bruker MI SE and Graphpad prism. The results of in vivo imaging detection and data analysis are shown in the figure. Figure 7 shown.

[0081] from Figure 7 It can be seen that CS-piscidin, Myr-CS and CS-RGD can significantly reduce the accumulation of tumor cells in mice, among which Myr-CS exhibits superior cancer cell clearance ability in vivo.

[0082] In summary, the CS-piscidin peptide modified by Cyclo-RGDfk has a strong ability to eliminate ovarian cancer, and its toxicity to normal ovarian epithelial cells is also enhanced. The Myr-CS peptide obtained by modifying CS-RGD with myristic acid has a slightly weakened activity and reduced toxicity to normal cells. It has stronger targeting and higher safety, and has the effect of long-term inhibition of ovarian cancer cell proliferation. The peritoneal ovarian cancer mouse model also further proves the anti-tumor activity of Myr-CS peptide in vivo.

[0083] Although the embodiments of the present invention have been disclosed as above, they are not limited to the applications listed in the specification and the implementation modes, and they can be fully applied to various fields suitable for the present invention. For those familiar with the art, additional modifications can be easily implemented. Therefore, without departing from the general concept defined by the claims and the scope of equivalents, the present invention is not limited to the specific details and the illustrations shown and described herein.

Claims

1. A compound having anti-tumor activity, characterized in that: Has the following structural formula:

2. The method for preparing a compound having anti-tumor activity according to claim 1, characterized in that: The carboxyl group on the first amino acid at the C-terminus of the CS-piscidin polypeptide is linked to the amino group on the side chain of the Cyclo-RGDfk polypeptide to obtain the CS-RGD polypeptide; The amino group on the first amino acid at the N-terminus of the CS-RGD polypeptide is connected to the carboxyl group on the myristic acid to obtain the Myr-CS polypeptide, which is the compound with anti-tumor activity; The structural formula of the CS-piscidin polypeptide is: The structure of the Cyclo-RGDfk polypeptide is:

3. The use of the compound having antitumor activity according to claim 1 in the preparation of antitumor drugs, characterized in that: The tumor is leukemia or ovarian cancer.

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