CN111187303B - Platinum (II) complex with high antitumor activity of cryptolepine, and synthetic method and application thereof - Google Patents
Platinum (II) complex with high antitumor activity of cryptolepine, and synthetic method and application thereof Download PDFInfo
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- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 title claims abstract description 19
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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Abstract
The invention relates to a platinum (II) complex with high antitumor activity for cryptolepine, which has a chemical formula of [ Pt (T) R ] Cl, wherein a ligand T is a compound synthesized by cryptolepine derivatives and dimethyl pyridylamine derivatives, and R is halogen. The synthesis method of the complex is that the cryptolepine derivative and the lutidine derivative react in the presence of a solvent and strong base to generate a yellow solid powder ligand T; the T ligand and the platinum (II) compound with the same amount of substances are subjected to coordination reaction in the presence of a polar solvent to obtain a yellow target product platinum (II) complex of the picrinine. The platinum (II) coordination compound of the cryptolepine shows excellent in-vivo and in-vitro anti-tumor activity and targeting property, has potential medicinal value, and is expected to be used for preparing various anti-tumor medicaments.
Description
Technical Field
The invention relates to a complex, in particular to a platinum (II) complex of picrinine with high anti-tumor activity. Meanwhile, the invention also relates to a synthetic method and application of the complex.
Background
Cisplatin antineoplastic drugs are widely used in clinical treatment because of their unique antineoplastic mechanism, significant antineoplastic effect and broad antineoplastic spectrum (white N J, walker S, craig G E, et al, the states of platinum anticancer drugs in the clinical and clinical trials [ J ] Dalton transformations, 2010,39 (35): 8113-8127.). Currently, more than 50% of chemotherapy treatment regimens involve the use of platinum drugs, of which FDA-approved Cisplatin (CDDP), carboplatin (carboplatin) and oxaliplatin (oxaliplatin) are the mainstays of clinical chemotherapy regimens for malignant tumors, which cause tumor cell apoptosis mainly through interaction with tumor DNA (liufengfan, threo. And the platinum drugs on the market lack selectivity and have low bioavailability, have serious adverse reaction in the treatment process, are easy to cause drug resistance of tumor cells, cross drug resistance and the like, and limit the further expanded application of the platinum drugs. In order to overcome the clinical defects of the classical cisplatin drugs, scholars at home and abroad synthesize a large amount of platinum complexes on the basis of the structures of the platinum antitumor drugs on the market so as to obtain the antitumor platinum drugs with higher biological activity, lower toxicity and overcome drug resistance or cross drug resistance.
The Sinomenine alkaloid has wide physiological activities of antibiosis, antivirus, antitrypanosoma, anti-inflammation and the like, and no metal complex reported by taking the Sinomenine and the derivative as ligands exists.
Disclosure of Invention
One of the purposes of the invention is to provide a platinum (II) complex of the cryptolepine with high anti-tumor activity.
Specifically, the platinum (II) complex of the cryptolepine with high anti-tumor activity has a chemical formula of [ Pt (T) R ] Cl (T-Pt for short), and the chemical structural formula is shown as the following formula:
wherein, the ligand Tm is a compound synthesized by the leafvine derivative and the bipyridine methylamine derivative, n is a natural number which is not zero, and R is halogen.
The second purpose of the invention is to provide a method for synthesizing platinum (II) coordination compound of the picrinine with high anti-tumor activity.
Specifically, the synthesis method of the platinum (II) complex of the cryptolepine with high anti-tumor activity comprises the following steps:
(1) Reacting a byttnerine derivative (SM) with a lutidine amine derivative in the presence of a solvent and strong base to generate a yellow solid powder ligand T;
(2) Ligand T and platinum (II) compound with the same amount of substance are subjected to coordination reaction in the presence of a polar solvent to obtain a yellow target product, namely platinum (II) chelerythrine complex T-Pt.
The synthetic route of the invention is as follows:
the structural formula of the lutidine amine derivative is as follows:
n is a natural number different from zero.
In the step (1), the molar ratio of the cryptolepine derivative (SM) to the lutidine amine derivative is 1-1.5.
In the step (1), the cryptolepine derivative (SM) and the lutidine derivative react for 1-10 hours at 20-30 ℃.
In step (2), platinum (II) compounds include, but are not limited to, dichloro-bis (dimethyl sulfoxide) platinum (II) solid (Pt (DMSO) 2 Cl 2 )。
In the step (2), the coordination reaction temperature is 30-100 ℃, and the reaction time is 10-80h.
In the step (2), the polar solvent is any one of methanol, ethanol, water, dimethyl sulfoxide and acetone or a mixed solution of two solvents, wherein the two solvents in the mixed solution are in any ratio. As an embodiment of the present invention, the polar solvent is a mixed solution of methanol and water or acetone, or a mixed solution of ethanol and water or acetone, or a mixed solution of dimethyl sulfoxide and methanol or ethanol.
The invention also aims to provide application of the platinum (II) complex of the cryptolepine. In particular to application of the platinum (II) coordination compound of the byttnerine in preparing antitumor drugs. More specifically, an application of the celandine zinc-platinum (II) complex in preparation of a medicine for targeted therapy of breast cancer is provided.
The invention has the beneficial effects that:
compared with the prior art, the jatrorrhizine derivative active ligand T provided by the invention is used as a ligand to synthesize a platinum complex [ Pt (T) R ] of the jatrorrhizine derivative active ligand T]Cl (T-Pt). The inventor researches the activity and toxicity of the complex T-Pt on human cervical cancer cells HeLa, human breast cancer cells (MCF-7 and MDA-MB-231), human ovarian cancer drug-resistant strains SK-OV-3/DDP cells and human normal liver HL-7702 cellsAnd (4) sexual experiments. MTT experimental results show that the complex T-Pt has very high antitumor activity on human breast cancer cells HeLa, MCF-7, MDA-MB-231 and SK-OV-3/DDP, and the in vitro antitumor activity of the complex T-Pt is far greater than that of ligand T and a clinical classical metal-based anticancer drug cis-platinum; in addition, the toxicity of the complex T-Pt to the normal cell HL-7702 is very small (IC) 50 More than 100 mu M), shows good target inhibition of human breast cancer proliferation. The complex T-Pt shows excellent in vivo and in vitro anti-tumor activity and targeting property, has potential medicinal value and is expected to be used for preparing various anti-tumor medicaments.
Drawings
FIG. 1 is a hydrogen nuclear magnetic resonance spectrum of T3 obtained in example 1 of the present invention;
FIG. 2 is a carbon nuclear magnetic resonance spectrum of T3 prepared in example 1 of the present invention;
FIG. 3 is an electrospray mass spectrum of the complex T3-Pt prepared in example 1 of the present invention;
FIG. 4 is a NMR chart of T3-Pt obtained in example 1 of the present invention;
FIG. 5 is a NMR carbon spectrum of T3-Pt prepared in example 1 of the present invention;
FIG. 6 is a T4 NMR chart obtained in example 4 of the present invention;
FIG. 7 is a T4 NMR carbon spectrum of the product obtained in example 4 of the present invention;
FIG. 8 is an electrospray mass spectrum of a complex T4-Pt prepared in example 4 of the present invention;
FIG. 9 is a NMR chart of T4-Pt obtained in example 4 of the present invention;
FIG. 10 is a NMR carbon spectrum of T4-Pt obtained in example 4 of the present invention.
Detailed Description
The present invention will be further described with reference to the following examples, but the present invention is not limited to these examples.
The raw material, cryptolepine derivative SM, involved in the synthetic method of the present invention was prepared with reference to the existing literature (Gu, l. -q.; et al.j. Med.chem.,2005,48, 7315-7321.). In addition, di (dimethylsulfoxide) dichloro platinum (II) can be referred to the existing literature (Al-alaf, t.a.k.;et al transit met chem 1998,23, 403-406), abbreviated cis-PtCl in the present application 2 (DMSO) 2 Or PtCl 2 (DMSO) 2 。
Example 1
(1) Synthesis and characterization of ligand T3:
in a 25.0mL round bottom flask, 1.0mol of compound SM, 1.05mol of the lutidine amine derivative and 2.00mol of NaH were weighed and dissolved in a solution containing 5.0mL of Dimethylacetamide (DMA), and after 10.0 hours of reaction at 25.0 ℃, the T3 ligand was obtained as a yellow solid powder with a yield of 53.0%.
The resulting T3 was characterized:
(1) The NMR spectrum is shown in FIG. 1.
1 H NMR(400MHz,CHCl 3 -d)δ8.49(d,J＝4.9Hz,2H),8.35(dd,J＝8.0,17.5Hz,2H),8.20(d,J＝8.6Hz,1H),7.70(t,J＝7.7Hz,1H),7.65-7.54(m,4H),7.53-7.41(m,4H),7.12-7.06(m,2H),5.29(s,1H),4.93(t,J＝6.4Hz,2H),3.81(s,4H),2.61(t,J＝6.9Hz,2H),1.91(quin,J＝6.9Hz,2H),1.73-1.54(m,4H).
(2) NMR spectrum of carbon, as shown in FIG. 2.
13 C NMR(101MHz,CHCl 3 -d)δ159.99,158.66,147.38,144.12,136.31,134.51,130.58,128.64,128.42,124.76,123.48,123.19,122.86,122.33(d,J＝15.4Hz,1C),121.86,121.39,111.99,72.78,60.57,54.30,29.93,26.91,23.70.
(3) The results of elemental analysis are shown in Table 1.
Table 1 elemental analysis results of Compounds T3 and T3-Pt in the examples
Thus, the yellow target product obtained can be identified as compound T3, the structural formula of which is as follows:
(2) And (3) synthesizing and characterizing the complex T3-Pt:
1.0mmol of ligand T3 and 1.0mmol of bis (dimethyl sulfoxide) dichloroplatinum (II) solid (cis-Pt (DMSO) 2 Cl 2 ) Dissolving the target product in 30mL of a mixed solution of methanol and acetone (volume ratio is 20. The yield was 91.3%.
The obtained T3-Pt was identified:
(1) Electrospray mass spectrometry, the spectrum of which is shown in FIG. 3.
ESI-MS m/z:731.9[M-Cl] + Wherein M is the molecular weight of the compound T3-Pt.
(2) NMR spectrum as shown in FIG. 4.
1 H NMR(500MHz,DMSO-d 6 )δ8.76(dd,J＝5.8,1.6Hz,2H),8.29–8.22(m,3H),8.20(dd,J＝8.9,1.2Hz,1H),8.14–8.10(m,1H),7.79(d,J＝7.9Hz,2H),7.78–7.72(m,3H),7.65–7.60(m,2H),7.57(ddd,J＝8.2,6.7,1.2Hz,1H),7.53(ddd,J＝7.9,6.5,1.5Hz,1H),5.41(d,J＝15.9Hz,2H),4.89(d,J＝15.8Hz,2H),4.79(t,J＝6.1Hz,2H),3.15–3.07(m,2H),1.77(dq,J＝12.2,6.3Hz,2H),1.65(dq,J＝13.8,7.1Hz,2H),1.51(q,J＝7.8Hz,2H).
(3) NMR spectrum of carbon, as shown in FIG. 5.
13 C NMR(126MHz,DMSO-d 6 )δ166.34,158.54,149.44,148.79,147.20,143.63,141.73,134.33,131.75,129.11,128.93,125.76,125.61,124.41,123.91,122.87,122.51,122.30,121.12,112.87,72.78,68.29,64.57,40.92,40.51,40.34,40.18,40.01,39.84,39.68,39.51,29.47,27.13,22.94.
(4) The results of elemental analysis are shown in Table 1.
Therefore, the obtained yellow target product can be determined to be a complex T3-Pt, and the structural formula of the complex is as follows:
example 2
1.0mmol of ligand T3 and 1.0mmol of bis (dimethyl sulfoxide) platinum (II) dichloride solid (Pt (DMSO) 2 Cl 2 ) Dissolving the target product in 15mL of mixed solution of ethanol and dimethyl sulfoxide (volume ratio is 2. The yield was 75.2%.
Example 3
1.0mmol of ligand T3 and 1.0mmol of bis (dimethyl sulfoxide) dichloroplatinum (II) solid (Pt (DMSO) 2 Cl 2 ) Dissolving the target product in 80mL of a mixed solution of ethanol and acetone (volume ratio is 50. The yield was 88.3%.
Experimental example 1
Experiment on proliferation inhibition activity of platinum (II) chelidonine complex T3-Pt on various human tumor cell strains
1. Cell lines and cell cultures
The experiment selects 5 human cell strains such as human cervical carcinoma HeLa cells, human ovarian cancer cisplatin drug-resistant SK-OV-3/DDP cells, human breast cancer cells (MCF-7 and MDA-MB-231) and human normal liver HL-7702 cells.
All human cell lines were cultured in RPMI-1640 medium containing 100U/mL penicillin, 10wt% calf blood and 100U/mL streptomycin, and the medium was adjusted to 37 ℃ with a volume concentration of 5% CO 2 Culturing in an incubator.
2. Preparation of test Compounds
The purity of the ligand T3 and the complex T3-Pt is required to be more than or equal to 95 percent, the DMSO stock solutions of the ligand T3 and the complex T3-Pt are diluted into a final solution of 20 mu mol/L (the final concentration of DMSO is less than or equal to 1 percent) by using a physiological buffer solution, and the inhibition degree of each compound on the growth of normal cells or selected tumor cells under the concentration is tested.
3. Cell growth inhibition assay (MTT method)
(1) Taking normal cells or tumor cells in logarithmic phase, digesting with trypsin, preparing a cell suspension with the concentration of 5000/mL by using a culture solution containing 10% calf serum, inoculating 190 mu L of the cell suspension into a 96-hole culture plate per hole, and enabling the density of cells to be detected to be 1000-10000 holes (the edge holes are filled with sterile PBS);
(2)5％CO 2 incubating for 24h at 37 ℃ until a cell monolayer is paved on the bottom of each well, adding 10 mu L of medicine with a certain concentration gradient into each well, and arranging 4 compound wells in each concentration gradient;
(3)5％CO 2 incubating at 37 ℃ for 48 hours, and observing under an inverted microscope;
(4) Add 10. Mu.L of MTT solution (5 mg/mL PBS, i.e., 0.5% MTT) per well and continue incubation for 4h;
(5) Terminating the culture, carefully removing the culture solution in the wells, adding 150 μ L of DMSO into each well to sufficiently dissolve formazan precipitate, mixing uniformly with an oscillator, and measuring the optical density of each well with a microplate reader at a wavelength of 570nm and a reference wavelength of 450 nm;
(6) The zero-setting wells (culture medium, MTT, DMSO) and the control wells (cells, culture medium, MTT, drug dissolution medium of the same concentration, DMSO) were also set.
(7) The number of living cells was judged from the measured optical density values (OD values), and the larger the OD value, the stronger the cell activity. Using the formula:
calculating the inhibition rate of each compound on the growth of the selected cells, and calculating the IC of each tested ligand T3 and the complex T3-Pt on each selected cell strain by the Bliss method 50 The value is obtained. The results are shown in table 2 below.
TABLE 2 IC of ligand T3 and complex T3-Pt on various cell lines 50 Value (μ M)
Slave IC 50 According to the activity screening result, the complex T3-Pt is used for 4 tested human tumor cell strains (human cervical carcinoma HeLa cells and human ovaries)The proliferation inhibition activity of the cancer cisplatin-resistant SK-OV-3/DDP cells and human breast cancer cells (MCF-7 and MDA-MB-231)) is obviously higher than that of metal salt cis-Pt (DMSO) 2 Cl 2 The ligand T3 and the cisplatin embody the synergistic effect of the ligand T3 and a platinum central atom. MTT results show that the complex T3-Pt has high anti-tumor activity on human breast cancer cells HeLa, MCF-7, MDA-MB-231 and SK-OV-3/DDP, and the IC of the complex 50 The value range is 0.05-2.35 mu M, and the in vitro anti-tumor activity of the compound is far greater than that of T3 ligand and a clinical classical metal-based anti-cancer medicament cisplatin; in addition, the toxicity of the complex T3-Pt to the normal cell HL-7702 is very small (IC) 50 More than 100 MuM), which shows good target inhibition on the proliferation of human breast cancer. In a word, the complex T3-Pt shows excellent in-vivo and in-vitro anti-tumor activity and targeting property, has potential medicinal value and is expected to be used for preparing various anti-tumor medicaments.
Example 4
(1) Synthesis and characterization of ligand T4:
in a 50.0mL round bottom flask, 1.0mol of compound SM, 1.20mol of the lutidine amine derivative and 2.20mol of NaH were weighed and dissolved in a solution containing 5.0mL of Dimethylacetamide (DMA), and after 1.7 hours of reaction at 25.0 ℃, a yellow solid powder of T4 ligand was obtained with a yield of 61.0%.
The resulting T4 was characterized:
(1) The NMR spectrum is shown in FIG. 6.
1 H NMR(400MHz,CHCl 3 -d)δ8.48(br d,J＝4.4Hz,2H),8.35(t,J＝9.2Hz,2H),8.18(d,J＝8.6Hz,1H),7.68(dt,J＝1.3,7.7Hz,1H),7.64-7.57(m,3H),7.55-7.46(m,3H),7.46-7.38(m,1H),7.10(dd,J＝5.5,6.6Hz,2H),4.94(t,J＝6.5Hz,2H),3.78(s,4H),3.47(s,1H),2.57-2.44(m,2H),2.02-1.87(m,2H),1.65-1.44(m,4H),1.42-1.32(m,2H),1.32-1.19(m,6H).
(2) NMR spectrum of carbon, as shown in FIG. 7.
13 C NMR(101MHz,CHCl 3 -d)δ160.12,158.63,149.15-148.75(m,1C),147.29,144.22,136.37,134.48,130.59,128.48(d,J＝5.9Hz,1C),124.75,123.48,123.11,122.84,122.37(d,J＝18.3Hz,1C),121.85,121.38,111.97,72.95,60.48,54.53,50.57,30.09,29.63-29.17(m,1C),27.19(d,J＝24.9Hz,1C),25.91.
(3) The results of elemental analysis are shown in Table 3.
Table 3 elemental analysis results of Compounds T4 and T4-Pt in examples
Thus, the yellow target product obtained can be identified as compound T4, the structural formula of which is as follows:
(2) And (3) synthesizing and characterizing the complex T4-Pt:
1.0mmol of ligand T4 and 1.0mmol of bis (dimethyl sulfoxide) dichloroplatinum (II) solid (Pt (DMSO) 2 Cl 2 ) Dissolving the target product in 50mL of a mixed solution of methanol and water (volume ratio is 100. The yield is as follows: 90.9 percent.
The obtained T4-Pt was identified:
(1) Electrospray mass spectrometry, the spectrum of which is shown in FIG. 8.
ESI-MS m/z:788.0[M-Cl] + Wherein M is the molecular weight of the compound T4-Pt.
(2) NMR spectrum as shown in FIG. 9.
1 H NMR(500MHz,DMSO-d 6 )δ8.79(dt,J＝6.0,1.8Hz,2H),8.32–8.24(m,4H),8.17–8.11(m,1H),7.83(d,J＝7.9Hz,2H),7.77–7.73(m,2H),7.68–7.65(m,2H),7.55(dddd,J＝30.5,8.0,6.9,1.2Hz,2H),5.39(d,J＝15.7Hz,2H),4.95–4.81(m,4H),3.03–2.98(m,2H),1.84(dq,J＝13.6,6.7Hz,2H),1.46(q,J＝10.9,7.2Hz,4H),1.25(t,J＝7.2Hz,2H),1.16–1.07(m,6H).
(3) NMR spectrum of the sample, as shown in FIG. 10.
13 C NMR(126MHz,DMSO-d 6 )δ166.36,158.56,149.47,148.80,147.24,143.78,141.78,134.38,131.72,129.10,128.95,125.81,125.57,124.39,123.93,122.90,122.49,122.28,121.20,112.86,73.06,68.33,64.68,40.94,40.53,40.36,40.20,40.03,39.86,39.69,39.53,29.81,29.09,29.06,28.90,27.44,26.24,25.69.
(4) The results of elemental analysis are shown in Table 3.
Therefore, the obtained yellow target product can be determined to be the complex T4-Pt, and the structural formula of the complex is as follows:
example 5
1.0mmol of ligand T4 and 1.0mmol of bis (dimethyl sulfoxide) dichloroplatinum (II) solid (Pt (DMSO) 2 Cl 2 ) Dissolving the target product in 100mL of a mixed solution of ethanol and acetone (volume ratio of 100. The yield is as follows: 50.2 percent.
Example 6
1.0mmol of ligand T4 and 1.0mmol of bis (dimethyl sulfoxide) dichloroplatinum (II) solid (Pt (DMSO) 2 Cl 2 ) Dissolving the target product in 10mL of a mixed solution of methanol and acetone (volume ratio is 50. The yield is as follows: 80.0 percent.
Experimental example 2
Experiment of proliferation inhibition activity of platinum (II) coordination compound T4-Pt with high antitumor activity on various human tumor cell strains
1. Cell lines and cell cultures
The experiment selects 5 human cell strains such as human cervical carcinoma HeLa cells, human ovarian cancer cisplatin drug-resistant SK-OV-3/DDP cells, human breast cancer cells (MCF-7 and MDA-MB-231) and human normal liver HL-7702 cells.
All human cell lines were cultured in RPMI-1640 medium containing 100U/mL penicillin, 10wt% calf blood and 100U/mL streptomycin, at 37 ℃ with a volume concentration of 5% CO 2 Culturing in an incubator.
2. Preparation of test Compounds
The purity of the ligand T4 and the complex T4-Pt is required to be more than or equal to 95 percent, the DMSO stock solutions of the ligand T4 and the complex T4-Pt are diluted into a final solution of 20 mu mol/L (the final concentration of DMSO is less than or equal to 1 percent) by using a physiological buffer solution, and the inhibition degree of each compound on the growth of normal cells or selected tumor cells under the concentration is tested.
3. Cell growth inhibition assay (MTT method)
(1) Taking normal cells or tumor cells in logarithmic phase, digesting with trypsin, preparing a cell suspension with the concentration of 5000/mL by using a culture solution containing 10% calf serum, inoculating 190 mu L of the cell suspension into a 96-hole culture plate per hole, and enabling the density of cells to be detected to be 1000-10000 holes (the edge holes are filled with sterile PBS);
(2)5％CO 2 incubating for 24h at 37 ℃ until a cell monolayer is paved on the bottom of each well, adding 10 mu L of medicine with a certain concentration gradient into each well, and arranging 4 compound wells in each concentration gradient;
(3)5％CO 2 incubating at 37 ℃ for 48 hours, and observing under an inverted microscope;
(4) Add 10. Mu.L of MTT solution (5 mg/mL PBS, i.e., 0.5% MTT) per well and continue incubation for 4h;
(5) Terminating the culture, carefully removing the culture solution in the wells, adding 150 μ L of DMSO into each well to sufficiently dissolve formazan precipitate, mixing uniformly with an oscillator, and measuring the optical density of each well with a microplate reader at a wavelength of 570nm and a reference wavelength of 450 nm;
(6) Simultaneously, a zero setting hole (culture medium, MTT, DMSO) and a control hole (cells, culture solution, MTT, a drug dissolving medium with the same concentration, DMSO) are arranged.
(7) The number of living cells was judged from the measured optical density values (OD values), and the larger the OD value, the stronger the cell activity. Using the formula:
calculating the inhibition rate of each compound on the growth of the selected cells, and calculating the IC of each tested compound on each selected cell line by the Bliss method 50 The value is obtained. The results are shown in table 4 below.
TABLE 4 IC of ligand T4 and Complex T4-Pt on various cell lines 50 Value (μ M)
Slave IC 50 According to the result of activity screening, the proliferation inhibition activity of the complex T4-Pt on 4 tested human tumor cell strains (human cervical cancer HeLa cells, human ovarian cancer cisplatin-resistant SK-OV-3/DDP cells and human breast cancer cells (MCF-7 and MDA-MB-231)) is obviously higher than that of metal salt cis-Pt (DMSO) 2 Cl 2 The ligand T4 and the cisplatin embody the synergistic effect of the ligand T4 and a platinum central atom. The result of an activity screening experiment shows that the complex T4-Pt has high anti-tumor activity on human breast cancer cells HeLa, MCF-7, MDA-MB-231 and SK-OV-3/DDP, and the IC of the complex is 50 The value range is 0.01-1.89 mu M, and the in vitro antitumor activity of the compound is far greater than that of T4 ligand and a clinical classical metal-based anticancer drug cisplatin; in addition, the toxicity of the complex T4-Pt to the normal cell HL-7702 is small (IC) 50 More than 100 mu M), shows good target inhibition of human breast cancer proliferation. In a word, the complex T4-Pt shows excellent in-vivo and in-vitro anti-tumor activity and targeting property, has potential medicinal value and is expected to be used for preparing various anti-tumor medicaments.
Claims (1)
1. The application of the platinum (II) chelidonine complex in preparing the medicine for targeted therapy of breast cancer is characterized in that the platinum (II) chelidonine complex has the following chemical structural formula:
wherein m is a non-zero natural number, n is a non-zero natural number, and R is halogen.
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Application publication date: 20200522 Assignee: Guangxi Xinghui Technology Co.,Ltd. Assignor: Yulin Normal University Contract record no.: X2022450000344 Denomination of invention: Platinum (II) Complexes of Leucine with High Antitumor Activity and Their Synthesis and Application Granted publication date: 20221004 License type: Common License Record date: 20221219 |