CN105418490A - Application of nitrogen mustard based piperlongumine compound in medicine - Google Patents
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- 229960004961 mechlorethamine Drugs 0.000 title claims abstract description 18
- -1 piperlongumine compound Chemical class 0.000 title claims abstract description 13
- VABYUUZNAVQNPG-UHFFFAOYSA-N Piperlongumine Natural products COC1=C(OC)C(OC)=CC(C=CC(=O)N2C(C=CCC2)=O)=C1 VABYUUZNAVQNPG-UHFFFAOYSA-N 0.000 title abstract description 13
- WHAAPCGHVWVUEX-UHFFFAOYSA-N Piperlonguminine Natural products CC(C)CNC(=O)C=CC=CC1=CC=C2OCOC2=C1 WHAAPCGHVWVUEX-UHFFFAOYSA-N 0.000 title abstract description 13
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- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
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- 125000004429 atom Chemical group 0.000 claims description 3
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- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
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- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 230000000259 anti-tumor effect Effects 0.000 abstract description 8
- 238000011160 research Methods 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract 1
- 230000003211 malignant effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
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- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- 206010028980 Neoplasm Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
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- YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- 238000012360 testing method Methods 0.000 description 2
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
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- 238000002965 ELISA Methods 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 235000019510 Long pepper Nutrition 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 240000003455 Piper longum Species 0.000 description 1
- 241000242678 Schistosoma Species 0.000 description 1
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- 230000003187 abdominal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
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- 229940055695 pancreatin Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- MUUHXGOJWVMBDY-UHFFFAOYSA-L tetrazolium blue Chemical compound [Cl-].[Cl-].COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 MUUHXGOJWVMBDY-UHFFFAOYSA-L 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/86—Oxygen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides application of a nitrogen mustard based piperlongumine compound in medicine. On the basis of the research on the nitrogen mustard based piperlongumine compound for inhibiting the activity of malignant cells, it proves that the nitrogen mustard based piperlongumine compound has the good anti-tumor activity, and a new choice is provided for preparing anti-tumor medicine.
Description
Technical Field
The invention relates to application of a nitrogen mustard base piperlongumine compound in medicine, in particular to application of the nitrogen mustard base piperlongumine compound in treating malignant tumors.
Background
The fructus piperis longi is a perennial herbaceous vine, and the fruit cluster of the fructus piperis longi is taken as a medicine in traditional Chinese medicine, so that the fructus piperis longi is mainly used for treating abdominal psychroalgia, vomiting, diarrhea, migraine, nasosinusitis, external toothache, coronary heart disease and angina pectoris. Piperlongumine (Piperlongumine)
Is one of main effective components separated from long pepper, and belongs to alkaloid compounds. With the intensive research on the Piperlongumine, a plurality of pharmacological effects of the Piperlongumine are found. It has pharmacological activities of resisting platelet aggregation, relieving pain, resisting fungi, resisting schistosome, resisting anxiety and resisting depression. Particularly, the compound shows remarkable cytotoxic effect on a plurality of tumor cells, has very small toxicity on normal cells under the same concentration, and is an anti-tumor traditional Chinese medicine monomer with extremely potential and selective toxicity (Raj et a1.,2011, Nature 475: 231-. The research literature of the compound in foreign countries is increasing, and the compound gradually becomes one of the research hotspots in the field.
Since the advent of the earliest use of nitrogen mustard based drugs as antitumor alkylating agents in clinical applications, the development of novel nitrogen mustard based drugs has been long-standing. In the development process of nitrogen mustard drugs, how to reduce the toxicity of the drugs and increase the selectivity of the drugs on tumors by introducing a new drug carrier so as to improve the therapeutic index is a common effort direction of scientists in each country. Therefore, structural modification of nitrogen mustard compounds, especially modification of the carrier moiety, has been a hot area of research in medicinal chemistry.
So far, the application of nitrogen mustard based piperlongumine compounds in medicines is not seen.
Disclosure of Invention
The invention aims to provide application of nitrogen mustard based piperlongumine compounds, namely application in medicines, and provides a new medicine for treating malignant tumors.
The nitrogen mustard based piperlongumine compound is a compound shown in the following general formula (I):
wherein,
R1hydrogen atom, hydroxyl, methyl, methoxyl, ethoxyl, fluorine atom, chlorine atom, bromine atom, and trifluoromethoxy;
R2hydrogen atom, hydroxyl, methyl, methoxyl, ethoxyl, fluorine atom, chlorine atom, bromine atom, and trifluoromethoxy.
Furthermore, the invention provides application of the nitrogen mustard based piperlongumine compounds in medicines.
Further, the use is for the treatment of a malignant tumor.
Further, the malignant tumor is one of skin cancer, liver cancer, esophageal cancer, gastric cancer, leukemia, ovarian cancer, prostate cancer, lung cancer, colorectal cancer, pancreatic cancer, breast cancer or kidney cancer.
The inventor carries out deep research on the inhibitory activity of the nitrogen mustard base piperlongumine compounds on various malignant tumor cells, and the experimental result shows that the compounds can inhibit various malignant tumor cells, so that a new thought is provided for developing the compounds into a new anti-tumor medicament.
The foregoing aspects of the present invention will be described in further detail with reference to specific embodiments. This is not to be construed as limiting the invention.
Detailed Description
Example 1: compound DJBB-1Preparation of
The synthetic route is as follows:
the synthetic route of the intermediate 1 is shown in the reference (Liuwenhui et al, pharmaceutical science, 2014,49 (2): 217-224).
The synthetic route for intermediate 2 is described in the literature references (Shoujiao Peng et al, J. Med. chem.2015, 58, 5242-.
Synthetic routes to the compound DJBB-1 are described in the literature references (Shoujiao Peng et al, J. Med. chem.2015, 58, 5242-:
a flask was charged with 110 mmol of the starting material, 210 mmol of the intermediate, and CH2Cl210 ml of triethylamine and 10 ml of the mixture were stirred at room temperature for 10 hours. Followed by addition of saturated NH4Cl solution washing, CH2Cl2Extracting, washing with saturated brine, and MgSO4Drying and concentrating. The crude product is separated by column chromatography, and the yield is 65%.
1H NMR(400 MHz, CDCl3)：7.89 (d, J =15.6 Hz,1H), 7.60-7.54 (m, 2H),7.34 (d, J = 15.6 Hz,1H), 6.94-6.90 (m, 3H),6.05 (t, J = 9.6 Hz,1H), 4.05 (t, J = 6.4 Hz,2H), 3.85 (t, J＝7.6 Hz, 4H)，3.72(t, J＝7.6 Hz, 4H)，2.44 (m,2H)。
MS-ESI(m/z)：389.08 (M+NaTen pieces of cloth)。
Example 2 Compound DJBB-2Preparation of
The synthetic route is the same as that of the compound DJBB-1.
The yield of compound DJBB-2 was 60%.
1H NMR(400 MHz, CDCl3)：7.90 (d, J =15.6 Hz,1H),7.32 (d, J = 15.6 Hz,1H), 6.96-6.92 (m, 3H), 6.02 (t, J = 9.6Hz,1H), 4.06 (t, J = 6.4 Hz,2H), 3.89 (s,6H)，3.86(t, J＝7.6 Hz, 4H)，3.74 (t, J＝7.6Hz, 4H)，2.42 (m,2H)。
MS-ESI(m/z)：449.10 (M+NaTen pieces of cloth)。
Example 3 Compound DJBB-3Preparation of
The synthetic route is the same as that of the compound DJBB-1.
The yield of compound DJBB-3 was 56%.
1H NMR(400 MHz, CDCl3)：7.92 (d, J =15.6 Hz,1H),7.36 (d, J = 15.6 Hz,1H), 6.96-6.92 (m, 3H), 6.03 (t, J = 9.6Hz,1H), 4.03 (t, J = 6.4 Hz,2H)，3.82 (t, J＝7.6 Hz, 4H)，3.76(t, J＝7.6 Hz, 4H)，2.46 (m,2H)。
MS-ESI(m/z)：425.06 (M+NaTen pieces of cloth)。
Example 4 Compound DJBB-4Preparation of
The synthetic route is the same as that of the compound DJBB-1.
The yield of compound DJBB-4 was 72%.
1H NMR(400 MHz, CDCl3)：7.92 (d, J =15.6 Hz,1H),7.34 (d, J = 15.6 Hz,1H), 6.93-6.90 (m, 3H), 6.04 (t, J = 9.6 Hz,1H),4.08 (t, J = 6.4 Hz,2H)，3.86 (t, J＝7.6 Hz, 4H)，3.74(t, J＝7.6 Hz, 4H)，2.42 (m,2H), 2.35 (s,6H)。
MS-ESI(m/z)：417.11 (M+NaTen pieces of cloth)。
Example 5: antitumor Activity test of Compounds of the present invention
The compound of the invention is subjected to a tumor cell proliferation inhibition test by adopting a conventional MTT method (such as New drug pharmacology research method, 2007:242-243, compiled by Luqiu army).
RPMI-1640, DMEM, fetal bovine serum, pancreatin, etc. were purchased from Gibco BRL corporation (Invitrogen corporation, USA), and thiazole blue tetrazolium bromide (MTT), dimethyl sulfoxide (DMSO) were products of Sigma corporation (USA). The 2-formamido thienopyridine derivatives are purchased from Specs company (Netherlands) and are chemical standard substances, and are prepared into 20mg/mL storage solution by DMSO during in-vitro experiments, and the storage solution is placed in a refrigerator at 4 ℃ and kept away from light for standby, and is diluted to the required concentration by complete culture solution when being used.
The cell lines selected from human lung cancer cell line (A549), human breast cancer cell line (MCF-7), human colon cancer cell line (HCT-116) and human liver cancer cell line (HepG2) were purchased from American ATCC company.
Human lung cancer cell line (A549), human breast cancer cell line ((MCF-7) and human colon cancer cell line (HCT-116) are prepared from RPMI-1640 complete culture medium containing 10% fetal calf serum, 100U/mL penicillin and 100. mu.g/mL streptomycin, and 5% C02And cultured at 37 ℃.
Human hepatoma cell line (HepG2) was cultured in DMEM complete medium containing 10% fetal bovine serum, 100U/mL penicillin, 100. mu.g/mL streptomycin and 5% C02And cultured at 37 ℃.
MTT method, adjusting cell concentration to 1-2 × 10 with complete culture solution4The cells were inoculated in a 96-well plate at 200. mu.L/well and cultured overnight, and the next day, the cells were treated with different doses of 2-formamidothienopyridine derivatives (final concentrations of 20, 5, 1.25, 0.31g/mL, respectively), while a drug-free negative control group and an equal volume of solvent control group were provided, with a DMSO concentration of 0.1%, 5 multiple wells were provided for each dose, 37 ℃, 5% C02And (5) culturing. After 48h of culture, 20 μ L of 5mg/mL MTT reagent is added to each well, the culture is continued for 2-4h, the supernatant is discarded, 150 μ L of DMSO is added, the mixture is shaken and mixed for 15min, the absorbance (A) value (A value is in direct proportion to the number of living cells) is measured by an enzyme-linked immunosorbent assay (lambda =570nm), and the average value is taken.
Relative cell proliferation inhibition (%) = (control inhibition-experimental inhibition)/control inhibition × 100%. The experiment was repeated at least 3 times. The experimental data are expressed as mean ± sd and processed using SPSS13.0 statistical software. The measured data are tested by t, and the difference is statistically significant when P is less than 0.05. (the control group is a solvent control group, and the solvent control group is not specifically shown because it has no cell proliferation inhibitory effect)
The results are shown in Table 1. Wherein, the compound refers to the nitrogen mustard piperlongumine compound prepared in the corresponding example (such as the compound DJBB-1 in the example 1).
IC of Table 1 Compounds on 4 tumor cells50Value of (. mu.M)
As can be seen from Table 1, the piperlongumine compounds containing the nitrogen mustard group pharmacophore have good anti-tumor activity, and a plurality of compounds are higher than the piperlongumine of the existing anti-tumor compound.
Claims (3)
1. The application of the nitrogen mustard base piperlongumine compounds in the medicine is characterized in that the nitrogen mustard base piperlongumine compounds are compounds shown in the following general formula (I):
wherein,
R1is hydrogen atom, hydroxyl, methyl, methoxyl, ethoxyl, fluorine atom, chlorine atom, bromine atom, trifluoromethoxylA group;
R2hydrogen atom, hydroxyl, methyl, methoxyl, ethoxyl, fluorine atom, chlorine atom, bromine atom, and trifluoromethoxy.
2. Use according to claim 1, characterized in that the use in medicine is the treatment of malignant tumors.
3. The malignant tumor according to claim 2, which is one of skin cancer, liver cancer, esophageal cancer, stomach cancer, blood cancer, ovarian cancer, prostate cancer, lung cancer, colorectal cancer, pancreatic cancer, breast cancer or kidney cancer.
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| CN114524741A (en) * | 2022-02-15 | 2022-05-24 | 上海龙翔生物医药开发有限公司 | Synthesis process of antitumor drug melphalan |
| WO2022153306A1 (en) * | 2021-01-14 | 2022-07-21 | B. G. Negev Technologies And Applications Ltd., At Ben-Gurion University | Anti-quorum sensing, anti-biofilm, and inflammation attenuating compounds, compositions, and methods of using same |
| CN115894407A (en) * | 2022-11-14 | 2023-04-04 | 广东海洋大学 | CIT fluorophore of 1-furan and thienyl-2-alkenyl-1-ketone containing nitrogen mustard and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101810612A (en) * | 2009-12-22 | 2010-08-25 | 北京欧凯纳斯科技有限公司 | Application of Piperlongumine compounds for resisting platelet aggregation |
| CN102125552A (en) * | 2010-01-20 | 2011-07-20 | 李绍路 | Use of piperlongumine derivatives in preparation of medicines for treating cancers and medicinal compositions thereof |
| CN102146054A (en) * | 2010-02-10 | 2011-08-10 | 新昌县来益科技开发有限公司 | Piperlongumine derivatives and medicinal composition and application to preparation of medicament for inhibiting tumor growth thereof |
| US20130203757A1 (en) * | 2009-09-02 | 2013-08-08 | The General Hospital Corporation | Compounds And Compositions For Treating Cancer |
| US20140024639A1 (en) * | 2012-07-20 | 2014-01-23 | The Broad Institute, Inc. | Compounds, Compositions, and Methods for Cancer Therapy |
-
2015
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130203757A1 (en) * | 2009-09-02 | 2013-08-08 | The General Hospital Corporation | Compounds And Compositions For Treating Cancer |
| CN101810612A (en) * | 2009-12-22 | 2010-08-25 | 北京欧凯纳斯科技有限公司 | Application of Piperlongumine compounds for resisting platelet aggregation |
| CN102125552A (en) * | 2010-01-20 | 2011-07-20 | 李绍路 | Use of piperlongumine derivatives in preparation of medicines for treating cancers and medicinal compositions thereof |
| CN102146054A (en) * | 2010-02-10 | 2011-08-10 | 新昌县来益科技开发有限公司 | Piperlongumine derivatives and medicinal composition and application to preparation of medicament for inhibiting tumor growth thereof |
| US20140024639A1 (en) * | 2012-07-20 | 2014-01-23 | The Broad Institute, Inc. | Compounds, Compositions, and Methods for Cancer Therapy |
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| WO2022153306A1 (en) * | 2021-01-14 | 2022-07-21 | B. G. Negev Technologies And Applications Ltd., At Ben-Gurion University | Anti-quorum sensing, anti-biofilm, and inflammation attenuating compounds, compositions, and methods of using same |
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| CN115894407A (en) * | 2022-11-14 | 2023-04-04 | 广东海洋大学 | CIT fluorophore of 1-furan and thienyl-2-alkenyl-1-ketone containing nitrogen mustard and preparation method and application thereof |
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