CN114569620A - Application of reagent based on tropolone compounds in preparation of tumor treatment drugs - Google Patents

Application of reagent based on tropolone compounds in preparation of tumor treatment drugs Download PDF

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CN114569620A
CN114569620A CN202210388783.XA CN202210388783A CN114569620A CN 114569620 A CN114569620 A CN 114569620A CN 202210388783 A CN202210388783 A CN 202210388783A CN 114569620 A CN114569620 A CN 114569620A
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hinokitiol
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CN114569620B (en
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李宽钰
赵洪婷
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Abstract

The invention provides an application of a tropolone compound-based reagent in preparation of a tumor treatment drug, belonging to the technical field of medicinal chemistry. In the invention, hinokitiol (hinokitiol) and iron ions are used together or hinokitiol and iron ions are utilized to form a hinokitiol iron complex, which can trigger a large amount of active oxygen to be generated in tumor cells and can effectively inhibit the growth of the tumor cells; in addition, the hinokitiol iron complex and iron are used together, so that a high-efficiency anti-tumor synergistic effect can be exerted, the tumor killing capacity is further enhanced, and the tumor cell death is promoted.

Description

Application of reagent based on tropolone compounds in preparation of tumor treatment drugs
Technical Field
The invention relates to the technical field of medicinal chemistry, in particular to application of a reagent based on a tropolone compound in preparation of a medicament for treating tumors.
Background
Hinokitiol (Hinokitiol), also known as Hinokitiol, is a natural tropolone derivative that has a variety of biological properties, including anti-inflammatory, antimicrobial and anti-cancer potential. It has been shown that hinokitiol can modulate the ER signaling pathway in Estrogen Receptor (ER) positive human breast cancer cells (MCF-7) and the glycogen synthase kinase 3 β/β -catenin signaling pathway in basal-like breast cancer cells, and can also partially mimic the function of iron transporters, such as divalent metal ion transporter (DMT1) and iron exporter (FPN 1).
The existing cancer drug therapy includes chemotherapy drugs, targeted drugs and endocrine therapy drugs, wherein the targeted drugs have good treatment effect and small side effect and are widely concerned by researchers. But resistance is the most common problem during treatment. Therefore, finding a new drug for treating cancer with better tumor killing effect is a problem to be solved urgently.
Disclosure of Invention
The invention aims to provide an application of a reagent based on a tropolone compound in preparing a tumor treatment drug, and in the invention, hinokitiol and iron ions are used in a combined way or form a hinokitiol iron complex by utilizing the hinokitiol and the iron ions, which can effectively inhibit the growth of tumor cells; and the junenol iron complex and iron are used together, so that a high-efficiency anti-tumor synergistic effect can be exerted, the tumor killing capacity is further enhanced, and the tumor cell death is promoted.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an application of a reagent based on a tropolone compound in preparing a medicine for treating tumors, wherein the reagent based on the tropolone compound is a mixture containing hinokitiol and iron ions, or a hinokitiol iron complex, or a mixture containing a hinokitiol iron complex and iron ions;
the hinokitiol iron complex has a structure shown in a formula I:
Figure BDA0003594757540000021
preferably, when the tropolone compound-based agent is a mixture comprising hinokitiol and iron ions, the molar ratio of hinokitiol to iron ions is 1: (0.33-10).
Preferably, when the tropolone compound-based agent is a mixture comprising an iron hinokitiol complex and an iron ion, the molar ratio of the iron hinokitiol complex to the iron ion is 1: (0.1-10).
Preferably, the iron reagent providing the iron ions is an inorganic iron salt compound.
Preferably, the tumor comprises breast cancer, gastric cancer, hematologic tumor, liver cancer or colon cancer.
Preferably, the mass content of the active ingredients in the medicine is 50-80%.
Preferably, the preparation method of the hinokitiol iron complex comprises the following steps:
carrying out coordination reaction on hinokitiol and an iron source in an organic solvent to obtain the hinokitiol-iron complex.
Preferably, the iron source is an inorganic iron salt compound; the molar ratio of hinokitiol to the iron element in the iron source is 3: 1.
preferably, the organic solvent comprises dimethyl sulfoxide or ethanol; the dosage ratio of the hinokitiol to the organic solvent is 100 mmol: 1L of the compound.
Preferably, the temperature of the coordination reaction is 15-25 ℃ and the time is 120-180 min.
The invention provides an application of a tropolone compound-based reagent in preparing a tumor treatment drug. In the invention, the combination use of hinokitiol and iron ions or the formation of a hinokitiol iron complex by utilizing hinokitiol and iron ions can trigger a large amount of active oxygen generated in tumor cells, and can effectively inhibit the growth of the tumor cells. In addition, the junenol iron complex is combined with iron, so that the tumor killing capacity of the junenol iron complex can be further amplified, more oxidative stress is generated, and therefore the growth of tumor cells is effectively inhibited, and the death of the tumor cells is promoted.
Drawings
FIG. 1 is a diagram showing the structural formula and spectral characteristic absorption peaks of hinokitiol and iron complexes of hinokitiol, and the spectral absorption peaks and substance diagrams of cell lysates of human breast cancer cells treated with hinokitiol and iron, respectively;
FIG. 2 is a graph showing the results of the inhibition of human breast cancer cells and mouse breast cancer cells by sabinol;
FIG. 3 is a graph showing the results of the inhibition of human breast cancer cells by sabinol, the combination of sabinol and iron, the sabinol iron complex, and the combination of the sabinol iron complex and iron;
FIG. 4 is a diagram showing the results of the inhibition of human gastric cancer cells and human erythroleukemia cells by the iron complex of hinokitiol and the combination of iron and hinokitiol;
FIG. 5 is an optical microscopic view of the combination of iron hinokitiol complex with iron to induce MDA-MB-231 cell death;
FIG. 6 is a graph showing the effect of hinokitiol, ferric ammonium citrate, iron hinokitiol complex, and iron-in-hinokitiol complex on cell membrane integrity;
FIG. 7 is a graph of the effect of iron hinokitiol complex on GSDME shearing;
FIG. 8 is a graph showing the effect of hinokitiol alone and iron complex in combination on MDA-MB-231 cell oxidative stress.
Detailed Description
The invention provides an application of a reagent based on a tropolone compound in preparing a medicine for treating tumors, wherein the reagent based on the tropolone compound is a mixture containing hinokitiol and iron ions, or a hinokitiol iron complex, or a mixture containing a hinokitiol iron complex and iron ions;
the hinokitiol iron complex has a structure shown in a formula I:
Figure BDA0003594757540000031
in the invention, the combination use of hinokitiol and iron ion (III) or the formation of a hinokitiol iron complex by utilizing hinokitiol and iron ion can trigger a large amount of active oxygen generated in tumor cells, and the growth of the tumor cells can be effectively inhibited under the condition of low concentration. In addition, the junenol iron complex is combined with iron, so that the tumor killing capacity of the junenol iron complex can be further amplified, more oxidative stress is generated, and therefore the growth of tumor cells is effectively inhibited, and the death of the tumor cells is promoted.
In the present invention, when the tropolone compound-based agent is a mixture comprising hinokitiol and an iron ion, the molar ratio of hinokitiol to iron ion is preferably 1: (0.33 to 10), more preferably 1: (0.33-1).
In the present invention, when the tropolone compound-based agent is a mixture comprising an iron hinokitiol complex and an iron ion, the molar ratio of the iron hinokitiol complex to the iron ion is preferably 1: (0.1 to 10), more preferably 1: (0.5-5).
In the present invention, the iron reagent providing the iron ions is preferably an inorganic iron salt compound, and the inorganic iron salt compound preferably includes ferric nitrate, ferric chloride or ferric ammonium citrate, and more preferably ferric ammonium citrate.
In the present invention, the tumor preferably includes breast cancer, stomach cancer, hematological tumor, liver cancer or colon cancer.
In the invention, the mass content of the active ingredients in the medicine is preferably 50-80%; when the hinokitiol iron complex is used alone, the active ingredient is the hinokitiol iron complex; when the hinokitiol iron complex is used in combination with iron, the active ingredients are the hinokitiol iron complex and iron.
In the invention, the medicine also comprises pharmaceutically acceptable auxiliary materials, and the pharmaceutically acceptable auxiliary materials preferably comprise benzyl alcohol, ethanol, propylene glycol, polysorbate 80 or cyclodextrin.
In the present invention, the dosage form of the drug preferably includes an injection, an oral liquid, a tablet or a capsule.
In the invention, when the medicine is used for treating breast cancer, the effective dose of the medicine is preferably 5-10 mg/kg, and the administration method of the medicine preferably comprises intravenous injection or oral administration; when the medicine is used for treating gastric cancer, the effective dose of the medicine is preferably 2-10 mg/kg, and the administration method of the medicine preferably comprises intravenous injection or oral administration; when the medicine is used for treating the blood tumor, the effective dose of the medicine is preferably 2-5 mg/kg, and the administration method of the medicine preferably comprises intravenous injection.
In the present invention, the method for preparing the hinokitiol iron complex preferably comprises the steps of:
carrying out coordination reaction on hinokitiol and an iron source in an organic solvent to obtain the hinokitiol-iron complex.
In the present invention, the iron source is preferably an inorganic iron salt compound, and the inorganic iron salt compound preferably includes ferric ammonium citrate, ferric nitrate or ferric chloride, and more preferably ferric ammonium citrate. In the present invention, the molar ratio of hinokitiol to the iron element in the iron source is preferably 3: 1.
in the present invention, the organic solvent preferably includes dimethyl sulfoxide or ethanol, and more preferably ethanol. In the present invention, the ratio of the amount of hinokitiol to the organic solvent is preferably 6.24 mmol: 1 mL.
The method preferably comprises the steps of mixing hinokitiol with an organic solvent to obtain a hinokitiol solution, and then mixing the hinokitiol solution with an iron source to perform a coordination reaction. In the invention, the temperature of the coordination reaction is preferably 15-25 ℃, and the coordination reaction can be carried out at room temperature; the time is preferably 120-180 min, and more preferably 120 min. In the present invention, the coordination reaction is preferably carried out under shaking conditions.
After the coordination reaction, preferably filtering a product system obtained after the coordination reaction, washing the obtained solid material, and drying to obtain the hinokitiol iron complex; the reagent used for the washing is preferably ethanol.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
102.6mg (6.24mmol) of hinokitiol (Hino) and 56.22mg (2.08mmol) of ferric chloride (FeCl) were accurately weighed3) Adding 1mL of ethanol to dissolve the two, and reacting for 2 hours at room temperature by vortex oscillationThe crystals were separated out, filtered, washed with ethanol, and dried in a fume hood to obtain powdery substance of iron hinokitiol complex (Fe (Hino))3)。
In FIG. 1, A is the structural formula of hinokitiol and hinokitiol iron complex.
Accurately weighing 16.42mg (0.1mmol) of hinokitiol, adding 1mL of dimethyl sulfoxide (DMSO) to dissolve to obtain 100mM hinokitiol solution, and diluting with DMSO to obtain 3mM hinokitiol solution; 13.51mg of ferric chloride hexahydrate was precisely weighed, and 500. mu.L of double distilled water (ddH) was added2O) dissolving the ferric chloride solution to obtain a ferric chloride solution with the concentration of 100mM, and diluting the ferric chloride solution by adopting DMSO to obtain a ferric chloride solution with the concentration of 1 mM; precisely weighing 13.65mg of hinokitiol iron complex, adding 500 μ LDMSO to dissolve to obtain 50mM hinokitiol iron complex solution, and diluting with DMSO to obtain 1mM hinokitiol iron complex solution. B in FIG. 1 is a physical diagram of a hinokitiol solution (3mM), an iron chloride solution (1mM) and a hinokitiol iron complex solution (1mM), and characteristic absorption peaks of the three, and results show that the hinokitiol iron complex has a characteristic absorption peak at 420 nm.
Cell line and cell culture: the cells used in the experiment are human breast cancer cells MDA-MB-231; the cell culture conditions include: in CO2Culturing in an incubator at 37 deg.C with CO2The volume fraction is 5 percent, and the saturation humidity is reached; the cell culture medium is a DMEM culture medium containing 10% fetal calf serum and 1% double antibody; passaging was performed every 3 days.
Preparing single cell suspension from logarithmic growth phase cells, inoculating in 60mm culture dish, and placing in CO2Culturing in an incubator. The cells were divided into 4 groups and treated with media containing different reagents, in the case of groups: dimethyl sulfoxide, 100 mu M hinokitiol, 50 mu M ferric ammonium citrate, and a combination of 100 mu M hinokitiol and 50 mu M ferric ammonium citrate; after 24 hours of treatment, cell pellets are collected and lysed with a cell lysate to obtain a cell protein extract. FIG. 1C is a diagram showing cell lysates of cells treated with dimethyl sulfoxide, hinokitiol, and ferric ammonium citrate, respectively, and a combination of hinokitiol and ferric ammonium citrate, andthe characteristic absorption peaks of the four compounds show that the hinokitiol iron complex exists in the cell after the hinokitiol and iron are combined to treat the cell.
Comparative application example 1 inhibitory Effect of sabinenol on Breast cancer cell
Cell line and cell culture: the cells used in the experiment are human breast cancer cells MDA-MB-231 and MCF-7, mouse breast cancer cells 4T-1 and E0771; the cell culture conditions include: in CO2Culturing in an incubator at 37 deg.C with CO2The volume fraction is 5 percent, and the saturation humidity is reached; the cell culture medium is a DMEM culture medium containing 10% fetal calf serum and 1% double antibody; passaging was performed every 3 days.
Cell viability assay: preparing single cell suspension from cells in logarithmic growth phase, inoculating to 96-well plate with 5000 cells/100 μ L per well, and placing in CO2After culturing for 16 hours in an incubator, the supernatant was discarded, the medium containing various concentrations of hinokitiol (0, 10. mu.M, 25. mu.M, 50. mu.M and 100. mu.M) was replaced, after culturing for 24 hours, the culture supernatant was discarded, a new cell culture medium was replaced, and 10. mu.L CCK8 was added to each well to examine the cell viability.
FIG. 2 is a result chart of the inhibition effect of sabinenol on human breast cancer cells and mouse breast cancer cells, and the results show that the activity of human breast cancer cells and mouse breast cancer cells is remarkably reduced after the sabinenol is treated, and the higher the degree of sabinenol is, the more remarkable the activity reduction is.
Application example 1 Umbelliferol iron complex and its combined use with iron in inhibiting breast cancer cells
Cell line and cell culture: the cells used in the experiment are human breast cancer cells MDA-MB-231, and the cell culture conditions comprise: in CO2Culturing in an incubator at 37 deg.C with CO2The volume fraction is 5 percent, and the saturation humidity is reached; the cell culture medium is a DMEM culture medium containing 10% fetal calf serum and 1% double antibody; passaging was performed every 3 days.
Cell viability assay: preparing single cell suspension from cells in logarithmic growth phase, inoculating to 96-well plate with 5000 cells/100 μ L per well, and placing in CO2Culturing in incubator for 16 hr, discarding supernatant, treating with corresponding medicine respectively, and treating with cell treatment group containing：
Firstly, independently preparing hinokitiol (0, 3 mu M, 15 mu M, 30 mu M and 60 mu M);
hinokitiol and iron (ferric ammonium citrate, FAC) combined treatment group, the molar ratio of hinokitiol to iron is 3:1 (3. mu.M hinokitiol + 1. mu.M iron, 15. mu.M hinokitiol + 5. mu.M iron, 30. mu.M hinokitiol + 10. mu.M iron, 60. mu.M hinokitiol + 20. mu.M iron);
③ hinokitiol iron complex group (1 MuM, 5 MuM, 10 MuM, 20 MuM);
a sabinenol iron complex and iron combined treatment group (5. mu.M sabinenol iron complex + 1. mu.M iron, 5. mu.M sabinenol iron complex + 5. mu.M iron, 5. mu.M sabinenol iron complex + 10. mu.M iron, 5. mu.M sabinenol iron complex + 25. mu.M iron);
after the cells are cultured for 24 hours, removing culture supernatant, replacing a new cell culture medium, and adding 10 mu L of CCK8 into each hole to detect the cell activity; a DMSO blank was also set.
A in figure 3 is a result chart of the inhibition effect of hinokitiol, the combination of hinokitiol and iron and the hinokitiol iron complex on human breast cancer cells, and the result shows that the hinokitiol, the combination of iron and hinokitiol and the hinokitiol iron complex have a better tumor inhibition effect compared with the single use of hinokitiol, and simultaneously, when the hinokitiol and iron are jointly treated, the hinokitiol iron complex is formed in a cell culture medium according to the molar ratio of 3:1, so that the hinokitiol iron complex can play a role; fig. 3B is a graph showing the results of the activity effect of the iron treatment with different concentrations alone and the combined treatment of the iron complexes of hinokitiol and iron with different concentrations on human breast cancer cells, and the results show that the killing ability of the iron complexes of hinokitiol and iron to human breast cancer cells is enhanced in an iron concentration-dependent manner, that is, the higher the iron concentration is, the stronger the cell killing ability is.
Application example 2 iron sabinenol complex and its combined use with iron to inhibit gastric cancer cell and human erythroleukemia cell
Cell line and cell culture: the cells used in the experiment are human gastric cancer cell lines BGC823, SGC7901, MGC803 and human erythroleukemia cell K562, and the cell culture conditions comprise: in CO2Culturing in an incubator at 37 deg.C with CO2The volume fraction is 5 percent, and the saturation humidity is reached; human stomachThe culture medium of the cancer cell line cells is a DMEM culture medium containing 10% fetal calf serum and 1% double antibody; the culture medium of human erythroleukemia cells is 1640 culture medium containing 10% fetal calf serum and 1% double antibody; passaging was performed every 3 days.
Cell viability assay: preparing single cell suspension from cells in logarithmic phase, inoculating the single cell suspension to a 96-well plate, culturing at a concentration of 5000 cells/100 mu L/well in an incubator for 16 hours, discarding the supernatant, replacing a culture medium containing 3 mu M iron sabinenol complex and 6 mu M Ferric Ammonium Citrate (FAC) respectively, culturing for 24 hours, discarding the culture supernatant, replacing with a new cell culture medium, and adding 10 mu L CCK8 per well to detect cell viability.
FIG. 4 is a result chart of the inhibitory effect of the sabinenol iron complex and the combination of the sabinenol iron complex and iron on human gastric cancer cells and human erythroleukemia cells, and the results show that the sabinenol iron complex can significantly reduce the activity of human gastric cancer cells, and the sabinenol iron complex and iron have a better tumor inhibitory effect compared with the single use of the sabinenol iron complex.
Test example 1 iron sabinenol Complex induces apoptosis of tumor cells
Cell line and cell culture: the cells used in the experiment are human breast cancer cells MDA-MB-231, and the cell culture conditions comprise: in CO2Culturing in an incubator at 37 deg.C with CO2The volume fraction is 5 percent, and the saturation humidity is reached; the cell culture medium is a DMEM culture medium containing 10% fetal calf serum and 1% double antibody; passaging was performed every 3 days.
And (3) observing cell morphology: since the hinokitiol iron complex induces tumor cell death, the cell morphology was observed by an optical microscope. Preparing single cell suspension from cells in logarithmic growth phase, inoculating to 96-well plate with 5000 cells/100 μ L per well, and placing in CO2After culturing for 16 hours in an incubator, the supernatant was discarded, the medium containing 5. mu.M iron sabinenol complex and 5. mu.M ammonium ferric citrate was replaced, and culture was carried out for 24 hours with DMSO as a control, and the culture supernatant was discarded, and the cell morphology was observed by an optical microscope. FIG. 5 shows that the combination of iron and hinokitiol complex induces MDA-MB-231 cell deathObserving with optical microscope, wherein the left side is DMSO-treated picture, and the right side is junenol iron complex combined with iron; the results show that after the combination treatment of the hinokitiol iron complex and iron, MDA-MB-231 cells are swelled and deformed, bubbles are formed, and the forms of cell scorching appear.
Cell lactate dehydrogenase release assay: disruption of cell membrane integrity can lead to release of cytoplasmic contents such as Lactate Dehydrogenase (LDH); the content of LDH in the culture medium can judge the rupture condition of the cell membrane. Specifically, human breast cancer cells MDA-MB-231 growing in a logarithmic phase are taken to prepare single-cell suspension, the single-cell suspension is inoculated into a 96-well plate, 15 mu M hinokitiol treatment, 5 mu M ferric ammonium citrate treatment, 5 mu M hinokitiol iron complex treatment and 5 mu M hinokitiol iron complex combined 5 mu M ferric ammonium citrate treatment are respectively given, after 24-hour culture, cell culture supernatant is collected, 400g centrifugation is carried out for 5min to remove cell debris, and the supernatant is taken for LDH content detection; a DMSO blank was also set. FIG. 6 is a graph showing the effect of hinokitiol, ferric ammonium citrate, a hinokitiol iron complex, and the combination of a hinokitiol iron complex with iron on cell membrane integrity, showing that the levels of LDH in cell culture fluid increase significantly after treatment with the hinokitiol iron complex alone or in combination with iron, indicating significant cell death.
Western Blot detection of protein levels: GSDME and GSDMD are important proteins involved in apoptosis of cells. Studies have shown that caspase-3 activated during apoptosis can cleave the N-terminal fragment of GSDME, so that N-terminal GSDME translocates to cell membrane to form pore passage and convert apoptosis into pyro-death. Specifically, human breast cancer cells MDA-MB-231 growing in a logarithmic phase are taken to prepare single cell suspension, the single cell suspension is inoculated into a 6-well plate, 0 mu M, 10 mu M, 25 mu M and 50 mu M of hinokitiol iron complex are respectively given for treatment, cell precipitates are collected after 24 hours of culture, cell lysis is used for extracting protein, the protein concentration is measured by a Bradford method, and the equivalent protein in each group is taken for Western Blotting detection of related protein levels. FIG. 7 is a diagram showing the effect of hinokitiol iron complex on GSDME shearing, and the results show that the hinokitiol iron complex treatment increases the production of GSDME shearing bodies, which indicates that the hinokitiol iron complex treatment can promote the tumor cells to generate cell apoptosis, thereby realizing the tumor killing effect.
Test example 2 iron complexes of hinokitiol promote the production of active oxygen in tumor cells
And (3) detecting active oxygen of cells: taking human breast cancer cell MDA-MB-231 cells growing in the logarithmic phase to prepare single-cell suspension, inoculating the single-cell suspension into a 6-well plate, giving single cypress wood alcohol (15 mu M) and cypress wood alcohol iron complex (5 mu M) to be combined with ferric ammonium citrate (5 mu M), culturing for 12 hours, collecting cell suspension by trypsinization, carrying out cell staining by using an active oxygen fluorescent probe H2-DCFDA, incubating for 30 minutes, washing cells by using PBS buffer solution, centrifugally collecting cell sediment, resuspending the cells by using the PBS buffer solution, detecting the fluorescence intensity of H2-DCFDA by using a flow cytometer, and judging the active oxygen level.
Cell lipid peroxidation assay: taking human breast cancer cell MDA-MB-231 cells growing in logarithmic phase to prepare single-cell suspension, inoculating the single-cell suspension into a 6-well plate, giving single sabinenol (15 mu M) and sabinenol iron complex (5 mu M) to be treated in combination with ferric ammonium citrate (5 mu M), culturing for 12 hours, collecting cell suspension by trypsinization, staining cells by using a lipid peroxide fluorescent probe BODIPY-C11, incubating for 15min, washing the cells by using PBS buffer solution, centrifugally collecting cell precipitates, re-suspending the cells by using the PBS buffer solution, detecting the fluorescence intensity of the BODIPY-C11 FL-1 channel by using a flow cytometer, and judging the level of lipid peroxide.
FIG. 8 is a graph showing the effect of sabinenol alone and iron complex in combination on MDA-MB-231 cells undergoing oxidative stress, on the left side, on the change in intracellular reactive oxygen species, and on the right side, on the lipid peroxidation level. The results show that the levels of active oxygen and lipid peroxidation are not obviously changed in the sabinenol-treated MDA-MB-231 cells, but are remarkably increased in the sabinenol iron complex and iron-treated MDA-MB-231 cells, which indicates that the sabinenol iron complex and iron are combined to induce the generation of active oxygen in the cells and promote lipid peroxidation, thereby promoting cell death.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (10)

1. The application of a reagent based on a tropolone compound in preparing a medicine for treating tumors is characterized in that the reagent based on the tropolone compound is a mixture containing hinokitiol and iron ions, or is a hinokitiol iron complex, or is a mixture containing the hinokitiol iron complex and iron ions;
the hinokitiol iron complex has a structure shown in a formula I:
Figure FDA0003594757530000011
2. use according to claim 1, characterized in that, when the tropolone compound-based agent is a mixture comprising hinokitiol and iron ions, the molar ratio of hinokitiol to iron ions is 1: (0.33-10).
3. Use according to claim 1, characterized in that when the tropolone compound-based agent is a mixture comprising an iron complex of hinokitiol and iron ions, the molar ratio of iron complex of hinokitiol to iron ions is 1: (0.1-10).
4. Use according to claim 1, wherein the iron reagent providing the iron ions is an inorganic iron salt compound.
5. The use of any one of claims 1 to 4, wherein the tumor comprises breast cancer, gastric cancer, hematological tumor, liver cancer or colon cancer.
6. The use according to any one of claims 1 to 4, wherein the active ingredient is present in the medicament in an amount of 50 to 80% by mass.
7. The use as claimed in claim 1, wherein the method for preparing the hinokitiol iron complex comprises the steps of:
carrying out coordination reaction on hinokitiol and an iron source in an organic solvent to obtain the hinokitiol-iron complex.
8. Use according to claim 7, wherein the iron source is an inorganic iron salt compound; the molar ratio of hinokitiol to the iron element in the iron source is 3: 1.
9. use according to claim 7, wherein the organic solvent comprises dimethyl sulfoxide or ethanol; the dosage ratio of the hinokitiol to the organic solvent is 6.24 mmol: 1 mL.
10. The use according to claim 7, wherein the temperature of the coordination reaction is 15 to 25 ℃ and the time is 120 to 180 min.
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CN110870874A (en) * 2018-08-13 2020-03-10 中山大学 Medicine with antibacterial effect and application thereof

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CN110870874A (en) * 2018-08-13 2020-03-10 中山大学 Medicine with antibacterial effect and application thereof

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YASUMOTO等: "Induction of tumor-specific cytotoxicity and apoptosis by hydroxyketones", 《MEIKAI UNIV DENT J》 *

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