CN114656450A - Preparation method and application of N ^ N ^ N ligand with ultraviolet-visible absorption and fluorescence luminescence characteristics - Google Patents
Preparation method and application of N ^ N ^ N ligand with ultraviolet-visible absorption and fluorescence luminescence characteristics Download PDFInfo
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
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Abstract
The invention belong to that technical field of photosensitizer for photodynamic therapy, Particularly relates to a preparation method and application of an N ^ N ^ N ligand with ultraviolet-visible absorption and fluorescence luminescence characteristics, The N ^ N ^ N ligand disclosed by the invention is prepared by reacting 2, 2 ': 6', 2 "| terpyridine 4 '| formaldehyde with 1, 2, 3, 3 | tetramethyl-3H | indolium iodide or 1 | ethyl-2, 3, 3 | trimethyl-3H | indolium iodide or 1 | ethyliodide 2, 3, 3 | trimethylbenzoindole. Compared with the traditional N ^ N ^ N ligand, it has better ultraviolet-visible absorption and better fluorescence ability, and can effectively improve the optical properties of photosensitizer when used in the synthesis of metal complex photosensitizer, thus improving its photodynamic therapy effect; At the same time, the N ^ N ^ N ligand of the invention has strong growth inhibition ability for common human cervical cancer cell lines, and is helpful for developing high-efficiency anticancer drugs.
Description
Technical Field
The invention belongs to the technical field of photosensitizers for photodynamic therapy, and particularly relates to a preparation method and application of an N ^ N ligand with ultraviolet-visible absorption and fluorescence luminescence characteristics.
Background
Cancer is one of the most fatal diseases worldwide. The current traditional treatment for cancer mainly includes surgical resection, chemotherapy and radiotherapy. Photodynamic therapy (PDT) has been widely paid attention as a novel treatment method, because it has advantages of non-invasive, accurate space-time control, etc. compared with the conventional methods. Ideally, the Photosensitizer (PS) is negligible toxic in the dark, but can be activated by light irradiation of a specific wavelength to generate cytotoxic Reactive Oxygen Species (ROS). ROS can rapidly destroy nearby biomolecules (proteins, lipids, or nucleic acids, etc.) and ultimately lead to cell death. At present, although a variety of different PS have been reported, such as porphyrin, BODIPY, cyanine dyes, and the like. However, most PS's suffer from poor water solubility and photobleaching, resulting in their diminished effectiveness in PDT treatment of cancer. As an alternative, metal complexes such as ruthenium (Ru), iridium (Ir) complexes, and the like are considered as promising therapeutic agents, and exhibit very attractive photophysical characteristics such as high water solubility, good photostability, high ROS-generating ability, and the like. Therefore, PDT using metal complexes has attracted great interest. It is worth mentioning that the complex TLD-1433 has already completed phase II clinical trials as PS for PDT for bladder cancer, which greatly enhances the enthusiasm for the development of new metal complexes in PDT.
The ideal PS must have strong visible absorption, efficient intersystem crossing (ISC) efficiency, high ROS production, deep tissue penetration, and long wavelength excitation properties. Among them, long-wavelength excitation can minimize optical damage to normal tissues, and achieve good tissue penetration and excellent spatial resolution, and thus long-wavelength excitation of PS is essential to ensure effective therapeutic effects. Currently, a variety of metal complexes have been reported for photodynamic therapy, but most photosensitizers still require irradiation with short wavelength excitation of uv or visible light to generate ROS, which limits the use of PS in deep tissues and solid tumors due to tissue penetration depth issues. In order to solve the problem of tissue penetration depth, a Near Infrared Region (NIR) metal complex photosensitizer activated by a two-photon process is researched and developed, but the excitation efficiency is low, and the activation only occurs at the focus of high-intensity pulse laser. Thus, two-photon absorbing metal complex photosensitizers have certain drawbacks for PDT. It can be seen that the development of metal complexes that are directly activated at long wavelengths is promising for PDT.
Currently, conventional N ^ N ^ N ligands have limited application of N ^ N in PDT due to poor physicochemical properties (such as poor ultraviolet-visible absorption and fluorescence emission capabilities), and by introducing large conjugated structures into the ligands, the physicochemical properties of the ligands can be effectively improved; meanwhile, by introducing transition metal atoms and ligands to form complexes, the ISC (interference coordination index) capability of the metal complex photosensitizer can be improved, and the separation of HOMO (highest occupied molecular orbital) and LUMO (Low-lying molecular orbital) can be effectively enhanced. Therefore, the metal complex photosensitizer formed by the N ^ N ^ N ligand modified by a reasonable structure and the transition metal can obviously transfer the advantages of the transition metal complex and the charge of the long-life triple metal ligand (3MLCT) state and the strong pi-pi + transition of fluorescent molecules under long wavelength are combined, so that the fluorescent molecular has the characteristics of high ROS generation capacity and long wavelength excitation, and the PDT treatment effect of the fluorescent molecular can be remarkably improved. Therefore, there is a need to develop new N ^ N ligands to increase the UV-visible absorption and fluorescence emission capabilities of the N ^ N ligands to improve their role in photodynamic therapy.
Disclosure of Invention
To overcome the above-mentioned deficiencies of the prior art, it is a primary object of the present invention to provide a N ^ N ligand having UV-visible absorption and fluorescence emission characteristics.
The second purpose of the invention is to provide a preparation method of the N ^ N ligand with the ultraviolet-visible absorption and fluorescence luminescence characteristics.
A third object of the present invention is to provide the use of the above-mentioned N ^ N ligands with UV-visible absorption and fluorescence emission characteristics.
The first object of the present invention is achieved by the following technical solutions:
an N ^ N ligand with ultraviolet-visible absorption and fluorescence emission characteristics, the structure of the N ^ N ligand is shown as a formula I and/or a formula II and/or a formula III (the ligands shown as the formula I and/or the formula II and/or the formula III are respectively abbreviated as tpyCN1, tpyCN2 and tpyPCN):
the second object of the present invention is achieved by the following technical solutions:
the preparation method of the N ^ N ^ N ligand with the characteristics of ultraviolet visible absorption and fluorescence luminescence comprises the following specific steps: prepared by reacting 2,2 ', 6', 2 '-terpyridine-4' -formaldehyde with 1,2,3, 3-tetramethyl-3H-indolium iodide or 1-ethyl-2, 3, 3-trimethyl-3H-indole-1-onium iodide or 1-ethyl 2,3, 3-trimethylbenzindole iodide; the structures of the 2,2 '-terpyridine-4' -formaldehyde, the 1,2,3, 3-tetramethyl-3H-indolium iodide, the 1-ethyl-2, 3, 3-trimethyl-3H-indol-1-ium iodide and the 1-ethyl 2,3, 3-trimethylbenzindole iodide are respectively shown as a formula (1), a formula (2), a formula (3) and a formula (4):
preferably, the reaction is a heating reflux reaction, the reaction time is 18-20 hours, and the reaction temperature is 70-90 ℃. Specifically, the reaction time was 19 hours, and the reaction temperature was 80 ℃.
Preferably, the reaction is carried out under an inert gas range.
Preferably, the molar ratio of the 2,2 ': 6', 2 '-terpyridine-4' -carbaldehyde to 1,2,3, 3-tetramethyl-3H-indolium iodide or 1-ethyl-2, 3, 3-trimethyl-3H-indol-1-ium iodide or 1-ethyl 2,3, 3-trimethylbenzindole iodide is 1: 1.
Preferably, the solvent used for the reaction includes, but is not limited to, ethanol.
Preferably, the method further comprises the following steps of ethanol recrystallization purification and drying.
The third object of the present invention is achieved by the following technical solutions:
the N ^ N ^ N ligand with the characteristics of ultraviolet-visible absorption and fluorescence luminescence is applied to the preparation of a photodynamic therapy photosensitizer.
The N ^ N ^ N ligand with the characteristics of ultraviolet visible absorption and fluorescence luminescence is applied to the preparation of the anti-cervical cancer medicine.
Compared with the traditional N ^ N ^ N ligand, the N ^ N ligand has better ultraviolet visible absorption and fluorescence emission capability, and meanwhile, the N ^ N ^ N ligand has high curative effect when being applied to the treatment of cervical cancer, has important significance for researching efficient metal complex photosensitizer antitumor drugs and lays experimental and theoretical foundation for clinically developing novel metal antitumor drugs.
The N ^ N ^ N ligand with the characteristics of ultraviolet visible absorption and fluorescence luminescence is applied to the preparation of the medicine for inhibiting the proliferation of the cervical cancer cells.
Preferably, the cervical cancer cells include, but are not limited to, HeLa cells.
Research shows that the ligand has cytotoxicity to cervical cancer cell strain (HeLa cell) and is a high-efficiency anticancer drug with good prospect.
Compared with the prior art, the invention has the beneficial effects that:
the invention discloses an N ^ N ^ N ligand with ultraviolet visible absorption and fluorescence luminescence characteristics, which is prepared by reacting 2,2 ': 6', 2 '-terpyridine-4' -formaldehyde with 1,2,3, 3-tetramethyl-3H-indolium iodide or 1-ethyl-2, 3, 3-trimethyl-3H-indol-1-ium iodide or 1-ethyl 2,3, 3-trimethylbenzindole iodide. Compared with the traditional N ^ N ^ N ligand, the N ^ N ^ N ligand pair has better ultraviolet visible absorption and better fluorescence luminous capacity, is used for synthesizing a metal complex photosensitizer, and can effectively improve the optical property of the photosensitizer, thereby improving the photodynamic therapy effect of the photosensitizer; meanwhile, cell experiment results show that the synthesized N ^ N ^ N ligand has strong growth inhibition capacity on common human cervical cancer cell strains, and is beneficial to developing efficient anticancer drugs.
Drawings
FIG. 1 is a graph of the UV-visible absorption spectra of N ^ N ligands (tpyCN1 ligand, tpyCN2 ligand, and tpyPCN ligand) in eight different solvents;
FIG. 2 is a graph of the fluorescence spectra of N ^ N ligands (tpyCN1 ligand, tpyCN2 ligand, and tpyPCN ligand) in eight different solvents;
FIG. 3 shows cytotoxicity of N ^ N ^ N ligands (tpyCN1 ligand, tpyCN2 ligand and tpyPCN ligand) on cervical cancer cell lines (HeLa).
Detailed Description
The following further describes the embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, but the present invention is not limited thereto. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The experimental procedures in the following examples were carried out by conventional methods unless otherwise specified, and the test materials used in the following examples were commercially available by conventional methods unless otherwise specified.
Example 1 preparation of novel N ^ N ^ N ligands
(1) Synthesis method of tpyCN1 ligand
the structure of the tpyCN1 ligand is shown in formula I:
the synthesis of tpyCN1 ligand can be performed according to the following reaction scheme:
the specific synthesis method comprises the following steps: according to the reaction formula, a mixture of compound (1)2,2 ': 6', 2 '-terpyridine-4' -formaldehyde (0.523g,2mmol) and compound (2)1,2,3, 3-tetramethyl-3H-indolium iodide (0.602g,2mmol) is added into absolute ethyl alcohol (30mL) and heated to 80 ℃, the reaction is cooled to room temperature after being refluxed for 19 hours in the absence of light under an argon atmosphere, precipitates are filtered and washed by ethyl ether, the obtained crude product is recrystallized by ethyl alcohol to obtain orange-red crystals, and the obtained crystals are further dried to obtain 0.98g of orange-red powder, namely tpyCN1 ligand, wherein the yield of the ligand is 92%.
By characterization, the ligand has the formula C28H25IN4，ESIm/z(C28H25N4 +),calc:417.54；found:417.1H NMR(400MHz,DMSO-d6)δ9.09(s,2H),8.81(dt,J＝4.6,1.5Hz,2H),8.70(d,J＝1.1Hz,1H),8.68(d,J＝1.1Hz,1H),8.65(d,J＝16.6Hz,1H),8.13–8.04(m,3H),8.06–7.98(m,1H),7.98–7.90(m,1H),7.75–7.64(m,2H),7.59(ddd,J＝7.5,4.7,1.2Hz,2H),4.31(s,3H),1.86(s,6H)。
(2) Synthesis method of tpyCN2 ligand
the structure of the tpyCN2 ligand is shown in formula II:
the synthesis of the tpyCN2 ligand can be performed according to the following reaction scheme:
the specific synthesis method comprises the following steps: according to the above reaction formula, a mixture of compound (1)2,2 ': 6', 2 '-terpyridine-4' -formaldehyde (0.523g,2mmol) and compound (3) 1-ethyl-2, 3, 3-trimethyl-3H-indol-1-ium iodide (0.630g,2mmol) was added to absolute ethanol (30mL) and heated to 80 ℃, the reaction was cooled to room temperature after refluxing in the absence of light under an argon atmosphere for 19 hours, and the precipitate was washed with diethyl ether by filtration, the crude product obtained was recrystallized from ethanol to give orange-red crystals, which were further dried to give 1.11g of orange-red powder, i.e., tpyCN2 ligand, with a yield of 95.3%.
By characterization, the ligand has the formula C29H27IN4，ESIm/z(C29H27N4 +),calc:31.57；found:431.1H NMR(400MHz,DMSO-d6)δ9.10(s,2H),8.82(d,J＝4.7Hz,2H),8.74–8.65(m,3H),8.09(dd,J＝18.4,11.5Hz,4H),7.96(d,J＝6.4Hz,1H),7.73–7.67(m,2H),7.58(t,J＝6.2Hz,2H),4.90(q,J＝7.5Hz,2H),1.88(s,6H),1.54(t,J＝7.2Hz,3H)。
(3) Synthesis method of tpyPCN ligand
the structure of the tpyPCN ligand is shown as formula III:
the synthesis of tpyPCN ligands can be performed according to the following reaction scheme:
the specific synthesis method comprises the following steps: according to the above reaction scheme, a mixture of compound (1)2,2 ': 6, 2 ' -terpyridine-4 ' -carbaldehyde (0.523g,2.5mmol) and compound (4) 1-ethyl2, 3, 3-trimethylbenzindole iodide (0.730g,2.5mmol) was added to absolute ethanol (30mL) and heated to 80 ℃ under reflux in the absence of light under argon for 19 hours, the reaction was cooled to room temperature, and the precipitate was washed with diethyl ether by filtration, the crude product obtained was recrystallized from ethanol to give reddish brown crystals, which were further dried to obtain 0.7040g of reddish brown powder, i.e., tpypPCN ligand, in a yield of 46%.
By characterization, the ligand has the formula C33H29IN4，ESIm/z(C33H29N4 +),calc:481.24；found:481.1H NMR(400MHz,DMSO-d6)δ9.14(s,2H),8.85(d,J＝4.8Hz,2H),8.77(d,J＝16.0Hz,2H),8.73(s,1H),8.50(d,J＝8.5Hz,1H),8.36(d,J＝8.9Hz,1H),8.25(dd,J＝15.1,8.6Hz,2H),8.19–8.11(m,3H),7.86(t,J＝7.6Hz,1H),7.79(t,J＝7.5Hz,1H),7.68–7.60(m,2H),5.02(q,J＝7.3Hz,2H),2.11(s,6H),1.61(t,J＝7.2Hz,3H)。
Example 2 UV-Vis absorption Spectroscopy experiments with novel N ^ N ligands in eight different solvents
Analysis of the N ^ N ^ N ligands of the invention (tpyCN1 ligand, tpyCN2 ligand and tpyPCN ligand) in eight different solvents (DMSO, DMF, H) using UV-visible spectrophotometer2O、CH3OH、CH3CN、EG、EA、CH2Cl2) Ultraviolet and visible absorption spectrum of (1). The absorption capacity of the ligand in the UV-visible region was analyzed by comparison with the UV-visible absorption spectra of control 2,2 ', 6', 2 "-terpyridine (tpy) in eight different solvents.
The measurement experiment steps of the ultraviolet visible absorption spectrum are as follows:
1 preparing 10mM solution of tpy, tpyCN1, tpyCN2 and tpyPCN in DMSO solvent;
② eight different solvents (DMSO, DMF, H)2O、CH3OH、CH3CN、EG、EA、CH2Cl2) Diluting a solution of tpy, tpyCN1, tpyCN2 and tpyPCN (10mM) into a 10 mu M solution, and measuring the absorption intensity of the solution in the ultraviolet and visible light region in an ultraviolet spectrometer in the wavelength range of 250-700 nm.
As shown in figure 1, comparing the ultraviolet spectra of tpyCN1, tpyCN2 and tpyPCN ligand with the spectra of a reference tpy, the N ^ N ^ N ligand has wider absorption range and higher intensity in the ultraviolet and visible light region compared with the conventional tpyN ^ N ligand (tpy), is more beneficial to synthesizing a complex with wider absorption range to be used as a photosensitizer, and improves the absorption efficiency of the photosensitizer.
Example 3 fluorescence Spectroscopy experiments with novel N ^ N ^ N ligands in eight different solvents
The N ^ N ^ N ligands (tpyCN1 ligand, tpyCN2 ligand and tpyPCN ligand) of the present invention were analyzed in eight different solvents (DMSO, DMF, H) using a fluorescence spectrophotometer2O、CH3OH、CH3CN、EG、EA、CH2Cl2) Fluorescence emission spectrum in (1). The fluorescence emission capability of the ligand was analyzed by comparison with the fluorescence spectra of control 2,2 ', 6', 2 "-terpyridine (tpy) in eight different solvents.
Wherein, the steps of the fluorescence spectrum measurement experiment are as follows:
1 preparing 10mM solution of tpy, tpyCN1, tpyCN2 and tpyPCN in DMSO solvent;
② eight different solvents (DMSO, DMF, H)2O、CH3OH、CH3CN、EG、EA、CH2Cl2) Diluting the solution of tpy, tpyCN1, tpyCN2 and tpyPCN (10mM) into 10 mu M solution, and then performing fluorescence spectrometry on the solution at a wavelength range of 400-800 nm (lambda)ex365nm) was measured for fluorescence intensity.
As shown in FIG. 2, comparing the fluorescence spectra of tpyCN1, tpyCN2, tpyPCN ligands with the fluorescence spectrum of a control tpy, it can be seen that the N ^ N ligands of the present invention have stronger fluorescence intensity and are more favorable for synthesizing complexes to be used as photosensitizers than the conventional N ^ N ligands (tpy).
EXAMPLE 4 novel N ^ N ^ N ligands corresponding to chemotherapy for human cervical cancer
The anti-proliferative effects of N ^ N ^ N ligands of the invention (tpyCN1 ligand, tpyCN2 ligand and tpyPCN ligand) on human cervical cancer (HeLa) cells were analyzed using MTT colorimetry with 2,2 ': 6', 2 "-terpyridine (tpy) as control.
MTT, namely thiazole blue, is a tetrazolium salt, in living cells, succinate dehydrogenase in mitochondria can reduce MTT to generate blue-violet crystal formazan (soluble in dimethyl sulfoxide), and the product has an absorption peak at 595nm, so that an enzyme linked immunosorbent assay (ELISA) detector can be used for analyzing the proliferation condition of cells.
The procedure for the MTT assay was as follows:
restoring cells: taking HeLa tumor cells frozen by liquid nitrogen, quickly thawing, washing frozen stock solution by PBS, then culturing and subculturing by using fresh complete culture solution (DMEM culture medium + 10% fetal bovine serum + 1% penicillin-streptomycin mixed solution), and performing MTT (methyl thiazolyl tetrazolium) experiment after 2 times of subculturing.
② seed-plating: when the cells reached logarithmic growth phase, the cells were seeded at a cell density of 5000 cells/well into 96-well plates (100. mu.L of culture medium (fresh complete culture medium) per well), and then transferred to 37 ℃ with 5% CO2The incubator of (2).
③ administration: after the cells in the 96-well plate adhere to the wall, mother liquor of DMSO configured ligands (tpyCN1 ligand, tpyCN2 ligand and tpyPCN ligand) is sucked, diluted by culture medium and respectively configured into working solution with concentration gradients of 1000, 500, 100, 10, 01 and 0.1 mu M, 10 mu L of original culture medium in the 96-well plate is sucked out, then 10 mu L of ligand working solution with 6 concentration gradients are respectively added into the 96-well plate, the mixture is gently shaken to enable the final concentration gradients of the ligands to be 100, 50, 10, 1, 0.1 and 0.01 mu M, and then the mixture is incubated in a carbon dioxide incubator for 48 hours.
Fourthly, after 48 hours of incubation, adding 10 mu of LMTT (5mg/mL) into each hole, continuing incubation for 4 hours in a constant temperature incubator at 37 ℃, then sucking supernatant, adding 100 mu of dimethyl sulfoxide (DMSO) into each hole, and detecting A by an enzyme linked immunosorbent assay detector595nmAnd calculating the cell growth inhibition rate to obtain IC50The value is obtained.
As shown in figure 3, compared with the tpy ligand, the N ^ N ^ N ligand (the tpyCN1 ligand, the tpyCN2 ligand and the tpyPCN ligand) has better killing effect on human cervical cancer (HeLa cells), wherein the chemotherapeutic effect of the tpyCN1(3 mu M) is better than that of the tpyCN2(4.143 mu M), and the chemotherapeutic effect of the tpyCN2(4.143 mu M) is better than that of the tpyPCN (12.9 mu M), so that the ligand has better cytotoxic effect on the cervical cancer cells and has good application value on the development of a novel metal complex photosensitizer.
In conclusion, the N ^ N ^ N ligands (tpyCN1 ligand, tpyCN2 ligand and tpyPCN ligand) have better ultraviolet visible absorption and fluorescence emission capability compared with the traditional N ^ N ligands, have high curative effect when being applied to the treatment of cervical cancer (HeLa cells), have important significance for researching high-efficiency metal complex photosensitizer antineoplastic drugs and lay the experimental and theoretical basis for clinically developing novel metal antineoplastic drugs.
The embodiments of the present invention have been described in detail above, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, and the scope of protection is still within the scope of the invention.
Claims (10)
1. An N ^ N ligand with ultraviolet-visible absorption and fluorescence emission characteristics, wherein the structure of the N ^ N ligand is shown as formula I and/or formula II and/or formula III:
2. the method of claim 1, wherein the ligand is prepared by reacting 2,2 ': 6 ', 2 "-terpyridine-4 ' -carbaldehyde with 1,2,3, 3-tetramethyl-3H-indolium iodide or 1-ethyl-2, 3, 3-trimethyl-3H-indol-1-ium iodide or 1-ethylbenzindole 2,3, 3-trimethylbenz-indole iodide; the structures of the 2,2 '-terpyridine-4' -formaldehyde, the 1,2,3, 3-tetramethyl-3H-indolium iodide, the 1-ethyl-2, 3, 3-trimethyl-3H-indol-1-ium iodide and the 1-ethyl 2,3, 3-trimethylbenzindole iodide are respectively shown as a formula (1), a formula (2), a formula (3) and a formula (4):
3. the method for preparing the N ^ N ^ N ligand with the characteristics of ultraviolet-visible absorption and fluorescence emission according to claim 2, wherein the reaction is a heating reflux reaction, the reaction time is 18-20 hours, and the reaction temperature is 70-90 ℃.
4. The method of claim 2, wherein the molar ratio of 2,2 ': 6 ', 2 "-terpyridine-4 ' -carbaldehyde to 1,2,3, 3-tetramethyl-3H-indolium iodide or 1-ethyl-2, 3, 3-trimethyl-3H-indol-1-ium iodide or 1-ethyl2, 3, 3-trimethylbenzindole iodide is 1: 1.
5. The method of claim 2, wherein the reaction is performed in an inert gas range.
6. The method of claim 2, wherein the solvent used in the reaction includes but is not limited to ethanol.
7. The use of the N ^ N ^ N ligands with ultraviolet-visible absorption and fluorescence emission characteristics according to claim 1 for the preparation of photodynamic therapy photosensitizers.
8. The use of the N ^ N ^ N ligands with the characteristics of ultraviolet-visible absorption and fluorescence emission of claim 1 for preparing a medicament for resisting cervical cancer.
9. The use of the N ^ N ^ N ligands with the ultraviolet-visible absorption and fluorescence emission characteristics of claim 1 for preparing a medicament for inhibiting the proliferation of cervical cancer cells.
10. The use of claim 8, wherein the cervical cancer cells include but are not limited to HeLa cells.
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