CN111138478A - Tricyclohexyltin quinoxaline-2-formate complex and preparation method and application thereof - Google Patents
Tricyclohexyltin quinoxaline-2-formate complex and preparation method and application thereof Download PDFInfo
- Publication number
- CN111138478A CN111138478A CN201911366728.5A CN201911366728A CN111138478A CN 111138478 A CN111138478 A CN 111138478A CN 201911366728 A CN201911366728 A CN 201911366728A CN 111138478 A CN111138478 A CN 111138478A
- Authority
- CN
- China
- Prior art keywords
- quinoxaline
- complex
- tricyclohexyltin
- cdcl
- ppm
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- STDYPBXBZWQSGV-UHFFFAOYSA-M tricyclohexylstannyl quinoxaline-2-carboxylate Chemical compound C1CCC(CC1)[Sn](C2CCCCC2)(C3CCCCC3)OC(=O)C4=NC5=CC=CC=C5N=C4 STDYPBXBZWQSGV-UHFFFAOYSA-M 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 238000010668 complexation reaction Methods 0.000 title description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 54
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000007787 solid Substances 0.000 claims description 18
- WCMMILVIRZAPLE-UHFFFAOYSA-M cyhexatin Chemical compound C1CCCCC1[Sn](C1CCCCC1)(O)C1CCCCC1 WCMMILVIRZAPLE-UHFFFAOYSA-M 0.000 claims description 15
- UPUZGXILYFKSGE-UHFFFAOYSA-N quinoxaline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 claims description 12
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 11
- 206010017758 gastric cancer Diseases 0.000 claims description 11
- 201000011549 stomach cancer Diseases 0.000 claims description 11
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 10
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 10
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 10
- 201000010881 cervical cancer Diseases 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 201000005202 lung cancer Diseases 0.000 claims description 10
- 208000020816 lung neoplasm Diseases 0.000 claims description 10
- 238000000902 119Sn nuclear magnetic resonance spectroscopy Methods 0.000 claims description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 9
- 239000000706 filtrate Substances 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 230000001093 anti-cancer Effects 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- RNVJQUPAEIQUTC-UHFFFAOYSA-N tricyclohexyltin Chemical compound C1CCCCC1[Sn](C1CCCCC1)C1CCCCC1 RNVJQUPAEIQUTC-UHFFFAOYSA-N 0.000 claims description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- UPUZGXILYFKSGE-UHFFFAOYSA-M quinoxaline-2-carboxylate Chemical compound C1=CC=CC2=NC(C(=O)[O-])=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-M 0.000 claims 1
- 230000003595 spectral effect Effects 0.000 claims 1
- 238000001228 spectrum Methods 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 10
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 10
- 210000004027 cell Anatomy 0.000 description 30
- 229910052718 tin Inorganic materials 0.000 description 10
- 238000012360 testing method Methods 0.000 description 9
- 238000000921 elemental analysis Methods 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 6
- -1 alkyl tin Chemical compound 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 239000003446 ligand Substances 0.000 description 5
- 239000003560 cancer drug Substances 0.000 description 4
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 4
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003606 tin compounds Chemical class 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- AYOHIQLKSOJJQH-UHFFFAOYSA-N dibutyltin Chemical compound CCCC[Sn]CCCC AYOHIQLKSOJJQH-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000005918 in vitro anti-tumor Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001942 tin-119 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Images
Classifications
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/22—Tin compounds
- C07F7/2224—Compounds having one or more tin-oxygen linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a tricyclohexyl tin quinoxaline-2-formate complex as well as a preparation method and application thereof, and the complex is represented by the following structural formula (I)
Description
Technical Field
The invention relates to a tricyclohexyl tin quinoxaline-2-formate complex, a preparation method thereof and application of the complex in preparing an anti-tumor medicament.
Background
Since Brown's first discovery of organotin Carboxylates (CH)3CO2SnPh3) Since the composition has the bioactivity of inhibiting mouse tumors, scientists have paid extensive attention to the synthesis, structure and bioactivity research of organotin carboxylate complexes.However, the known organotin compounds are generally highly toxic and thus have limited applications. Research has shown that the structure, reactivity and biological activity of organotin compounds are related both to the structure of the hydrocarbon group directly attached to the tin atom and to the nature of the ligand. The optimization of the structure of the organic tin complex through molecular design so as to adjust the balance between the toxicity and the biological activity of the organic tin complex is an important direction of research of people at present. The functional activation of alkyl or ligand can greatly change the coordination mode of tin atom, and further influence the bioactivity of organic tin complex. Research shows that the toxicity of the organic tin compound is related to the relative molecular mass of the organic tin compound, the smaller the relative molecular mass is, the greater the toxicity is, and the larger the relative molecular mass of the large steric hindrance alkyl tin. Therefore, the novel alkyl tin complex with large steric hindrance is synthesized, and the structure and the biological activity of the complex are researched, so that the method has important research significance.
As is well known, nitrogen heterocycles are important and common structural units of medicines, pesticides, functional materials and the like, and most of them are closely related to life systems, so that the research on the structure of organotin derivatives of such ligands can not only provide useful information for the revealed anticancer mechanism, but also provide a possible molecular design scheme for the development of novel drugs. Nitrogen-containing heteroatom carboxylic acid is an important carboxylic acid ligand, and the synthesis of novel nitrogen-containing heterocyclic organic tin carboxylate compounds and the research on the biological activity of the nitrogen-containing heterocyclic organic tin carboxylate compounds are very necessary. For example, Chinese patent CN101402650B discloses the application of a dibutyltin and quinolinecarboxylic acid complex in preparing medicines for treating gastric cancer, nasopharyngeal carcinoma, human liver cancer or leukemia.
Based on that the tricyclohexyl tin hydroxide is a substance which is proved to have good biological activity by experiments, and the cyclohexyl has the characteristics of large steric hindrance, large molecular weight and the like, the tricyclohexyl tin hydroxide is selected to react with heterocyclic carboxylic acid ligand quinoxaline-2-formic acid under certain conditions to synthesize the complex with strong inhibitory activity to A549 (human lung cancer cells), Hela (human cervical cancer cells) and HGC-27 (human gastric cancer cells), thereby providing a new way for developing anticancer drugs.
Disclosure of Invention
In view of the problems of the prior art as described above, a first object of the present invention is to provide a tricyclohexyltin quinoxaline-2-carboxylate complex.
The second object of the present invention is to provide a process for the preparation of the above tricyclohexyltin quinoxaline-2-carboxylate complex.
The third purpose of the invention is to provide the application of the tricyclohexyl tin quinoxaline-2-formate complex in preparing an anti-cancer drug.
A tricyclohexyltin quinoxaline-2-carboxylate complex, as a first aspect of the present invention, is a complex of the following structural formula (I):
(I)。
the results of the tricyclohexyl tin quinoxaline-2-formic ether complex of the invention after element analysis, infrared spectrum analysis and nuclear magnetic resonance spectrum are as follows:
elemental analysis (C)27H38N2O2Sn): theoretical value: c, 59.91; h, 7.08; and N, 5.18. Measurement value: c, 59.93; h, 7.02; and N, 5.23.
IR(KBr, v/cm-1): 3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m)。
1H NMR(CDCl3, 500 MHz),δ(ppm):9.55(s, 1H), 8.32 (d,J=8Hz, 1H), 8.15(d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H), 1.81-1.64 (m, 15H),1.43-1.35(m, 9H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 168.01, 146.05, 144.88, 143.26,141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15, 28.93(t,J= 32 Hz),26.84。
119Sn NMR(CDCl3, 186 MHz), δ(ppm): 38.38。
The tricyclohexyl tin quinoxaline-2-formate complex has the structural characteristics that: the central tin in the molecule forms a distorted tetrahedral configuration with the coordinating atoms.
As a preparation method of the tricyclohexyl tin quinoxaline-2-formate complex, in a 250 mL round-bottom flask, tricyclohexyl tin hydroxide, quinoxaline-2-formic acid and a solvent toluene are sequentially arranged in sequence, a Dean-Stark water separator is arranged, and heating reflux reaction is carried out at 112-120 ℃ for 6-12 hours. After the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex.
In a preferred embodiment of the invention, the mass ratio of the tricyclohexyltin hydroxide to the quinoxaline-2-carboxylic acid is 1 (1-1.1).
In a preferred embodiment of the invention, the solvent toluene is added in an amount of 25-35 ml per millimole of tricyclohexyltin hydroxide.
The third aspect of the invention relates to the application of a tricyclohexyltin quinoxaline-2-formate complex in preparing an anti-cancer drug.
The applicant carries out in-vitro antitumor activity confirmation research on the complex, and confirms that the complex has certain antitumor biological activity, namely the application of the complex in preparing antitumor drugs, in particular in preparing anti-human lung cancer drugs, human cervical cancer drugs and human gastric cancer drugs.
The tricyclohexyltin quinoxaline-2-formate complex shows good anticancer activity on human lung cancer cells, human cervical cancer cells, human gastric cancer cells and the like, and can be used as a raw material for preparing anti-lung cancer, anti-cervical cancer and anti-gastric cancer drugs. Compared with the platinum anticancer drugs commonly used at present, the tricyclohexyl tin quinoxaline-2-formate complex has the characteristics of high anticancer activity, low cost, simple preparation method and the like, and provides a new way for developing anticancer drugs.
Drawings
FIG. 1 is an IR spectrum of a tricyclohexyltin quinoxaline-2-carboxylate complex.
FIG. 2 is a schematic representation of a tricyclohexyltin quinoxaline-2-carboxylate complex1H NMR spectrum.
FIG. 3 is a schematic representation of a tricyclohexyltin quinoxaline-2-carboxylate complex13C NMR spectrum.
FIG. 4 is a schematic representation of a tricyclohexyltin quinoxaline-2-carboxylate complex119Sn NMR spectrum.
Detailed Description
The present invention is further illustrated in detail by the following examples, but it should be noted that the scope of the present invention is not limited by these examples at all.
Example 1:
preparation of tricyclohexyl tin quinoxaline-2-carboxylate complex:
0.3851g (1mmol) of tricyclohexyltin hydroxide, 0.1743 g (1mmol) of quinoxaline-2-formic acid and 25 mL of solvent toluene are sequentially added into a 250 mL round-bottom flask, a Dean-Stark water separator is arranged, and the reaction is heated and refluxed at 120 ℃ for 6 hours. After the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex. Yield: 82%, melting point: 130 ℃ and 133 ℃.
Elemental analysis (C)27H38N2O2Sn): theoretical value: c, 59.91; h, 7.08; and N, 5.18. Measurement value: c, 59.93; h, 7.02; and N, 5.23.
IR(KBr, v/cm-1): 3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m)。
1H NMR(CDCl3, 500 MHz),δ(ppm):9.55(s, 1H), 8.32 (d,J=8Hz, 1H), 8.15(d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H), 1.81-1.64 (m, 15H),1.43-1.35(m, 9H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 168.01, 146.05, 144.88, 143.26,141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15, 28.93(t,J= 32 Hz),26.84。
119Sn NMR(CDCl3, 186 MHz), δ(ppm): 38.38。
Example 2:
preparation of tricyclohexyl tin quinoxaline-2-carboxylate complex:
3853g (1.0 mmol) of tricyclohexyltin hydroxide, 0.1915g (1.1 mmol) of quinoxaline-2-formic acid and 25 mL of solvent toluene are sequentially added into a 250 mL round-bottom flask, a Dean-Stark water separator is arranged, and the reaction is heated and refluxed at 120 ℃ for 8 hours. After the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex. Yield: 80%, melting point: 130 ℃ and 133 ℃.
Elemental analysis (C)27H38N2O2Sn): theoretical value: c, 59.91; h, 7.08; and N, 5.18. Measurement value: c, 59.93; h, 7.02; and N, 5.23.
IR(KBr, v/cm-1): 3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m)。
1H NMR(CDCl3, 500 MHz),δ(ppm):9.55(s, 1H), 8.32 (d,J=8Hz, 1H), 8.15(d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H), 1.81-1.64 (m, 15H),1.43-1.35(m, 9H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 168.01, 146.05, 144.88, 143.26,141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15, 28.93(t,J= 32 Hz),26.84。
119Sn NMR(CDCl3, 186 MHz), δ(ppm): 38.38。
Example 3:
preparation of tricyclohexyl tin quinoxaline-2-carboxylate complex:
0.3851g (1.0 mmol) of tricyclohexyltin hydroxide, 0.1916g (1.1 mmol) of quinoxaline-2-carboxylic acid and 35 mL of solvent toluene are sequentially added into a 250 mL round-bottom flask, a Dean-Stark water separator is arranged, and the reaction is heated and refluxed at 120 ℃ for 8 hours. After the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex. Yield: 82%, melting point: 130 ℃ and 133 ℃.
Elemental analysis (C)27H38N2O2Sn): theoretical value: c, 59.91; h, 7.08; and N, 5.18. Measurement value: c, 59.93; h, 7.02; and N, 5.23.
IR(KBr, v/cm-1):3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m)。
1H NMR(CDCl3, 500 MHz),δ(ppm):9.55(s, 1H), 8.32 (d,J=8Hz, 1H), 8.15(d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H), 1.81-1.64 (m, 15H),1.43-1.35(m, 9H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 168.01, 146.05, 144.88, 143.26,141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15, 28.93(t,J= 32 Hz),26.84。
119Sn NMR(CDCl3, 186 MHz), δ(ppm): 38.38。
Example 4:
preparation of tricyclohexyl tin quinoxaline-2-carboxylate complex:
0.7709g (2.0mmol) of tricyclohexyltin hydroxide, 0.3654g (2.1 mmol) of quinoxaline-2-carboxylic acid and 50 mL of solvent toluene are sequentially added into a 250 mL round-bottom flask, a Dean-Stark water separator is arranged, and the reaction is heated and refluxed at 120 ℃ for 8 hours. After the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex. Yield: 83%, melting point: 130 ℃ and 133 ℃.
Elemental analysis (C)27H38N2O2Sn): theoretical value: c, 59.91; h, 7.08; and N, 5.18. Measurement value: c, 59.93; h, 7.02; and N, 5.23.
IR(KBr, v/cm-1): 3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m)。
1H NMR(CDCl3, 500 MHz),δ(ppm):9.55(s, 1H), 8.32 (d,J=8Hz, 1H), 8.15(d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H), 1.81-1.64 (m, 15H),1.43-1.35(m, 9H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 168.01, 146.05, 144.88, 143.26,141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15, 28.93(t,J= 32 Hz),26.84。
119Sn NMR(CDCl3, 186 MHz), δ(ppm): 38.38。
Example 5:
preparation of tricyclohexyl tin quinoxaline-2-carboxylate complex:
0.7701g (2.0mmol) of tricyclohexyltin hydroxide, 0.3485g (2.0mmol) of quinoxaline-2-formic acid and 60 mL of solvent toluene are sequentially added into a 250 mL round-bottom flask, a Dean-Stark water separator is arranged, and the reaction is heated and refluxed at 120 ℃ for 12 hours. After the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex. Yield: 82%, melting point: 130 ℃ and 133 ℃.
Elemental analysis (C)27H38N2O2Sn)：Theoretical value: c, 59.91; h, 7.08; and N, 5.18. Measurement value: c, 59.93; h, 7.02; and N, 5.23.
IR(KBr, v/cm-1): 3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m)。
1H NMR(CDCl3, 500 MHz),δ(ppm):9.55(s, 1H), 8.32 (d,J=8Hz, 1H), 8.15(d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H), 1.81-1.64 (m, 15H),1.43-1.35(m, 9H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 168.01, 146.05, 144.88, 143.26,141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15, 28.93(t,J= 32 Hz),26.84。
119Sn NMR(CDCl3, 186 MHz), δ(ppm): 38.38。
Example 6:
preparation of tricyclohexyl tin quinoxaline-2-carboxylate complex:
1.1551g (3.0 mmol) of tricyclohexyltin hydroxide, 0.5224g (3.0 mmol) of quinoxaline-2-carboxylic acid and 75 mL of solvent toluene are sequentially added into a 250 mL round-bottom flask, a Dean-Stark water separator is arranged, and the reaction is heated and refluxed at 120 ℃ for 12 hours. After the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex. Yield: 84%, melting point: 130 ℃ and 133 ℃.
Elemental analysis (C)27H38N2O2Sn): theoretical value: c, 59.91; h, 7.08; and N, 5.18. Measurement value: c, 59.93; h, 7.02; and N, 5.23.
IR(KBr, v/cm-1): 3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m)。
1H NMR(CDCl3, 500 MHz),δ(ppm):9.55(s, 1H), 8.32(d,J=8Hz, 1H), 8.15(d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H), 1.81-1.64 (m, 15H),1.43-1.35(m, 9H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 168.01, 146.05, 144.88, 143.26,141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15, 28.93(t,J= 32 Hz),26.84。
119Sn NMR(CDCl3, 186 MHz), δ(ppm): 38.38。
Example 7:
preparation of tricyclohexyl tin quinoxaline-2-carboxylate complex:
1.1553 g (3.0 mmol) of tricyclohexyltin hydroxide, 0.5748g (3.3 mmol) of quinoxaline-2-carboxylic acid and 90 mL of solvent toluene are sequentially added into a 250 mL round-bottom flask, a Dean-Stark water separator is arranged, and the reaction is heated and refluxed at 120 ℃ for 6 hours. After the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex. Yield: 82%, melting point: 130 ℃ and 133 ℃.
Elemental analysis (C)27H38N2O2Sn): theoretical value: c, 59.91; h, 7.08; and N, 5.18. Measurement value: c, 59.93; h, 7.02; and N, 5.23.
IR(KBr, v/cm-1): 3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m)。
1H NMR(CDCl3, 500 MHz),δ(ppm):9.55(s, 1H), 8.32 (d,J=8Hz, 1H), 8.15(d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H), 1.81-1.64 (m, 15H),1.43-1.35(m, 9H)。
13C NMR(CDCl3, 125 MHz),δ(ppm): 168.01, 146.05, 144.88, 143.26,141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15,28.93(t,J= 32 Hz),26.84。
119Sn NMR(CDCl3, 186 MHz), δ(ppm): 38.38。
Test example:
the in vitro anticancer activity determination of the tricyclohexyl tin quinoxaline-2-formate complex is realized by an MTT experimental method.
MTT assay:
based on the metabolic reduction of 3- (4, 5-dimethylthiozol-2-yl) -2, 5-diaryltetrazolium bromide. Succinate dehydrogenase in mitochondria of living cells can reduce exogenous MTT to water-insoluble blue-purple crystalline Formazan (Formazan) and deposit in cells, while dead cells do not have this function. Dimethyl sulfoxide (DMSO) can dissolve formazan in cells, and the optical density of characteristic wavelength is measured by enzyme labeling instrument, which can indirectly reflect the number of living cells.
MTT method was used to determine the inhibitory activity of the tricyclohexyltin quinoxaline-2-carboxylate complex prepared in example 1 on human lung cancer cells (A549), human cervical cancer cells (Hela), and human gastric cancer cells (HGC-27).
Cell line and culture System: the A549, Hela and HGC-27 cell lines were obtained from the American tissue culture Bank (ATCC). Using RPMI1640 medium (GIBICO) containing 10% fetal bovine serum at 5% (volume fraction) CO2And culturing in vitro in a 37 ℃ saturated humidity incubator.
The testing process comprises the following steps: and respectively adding the test liquid medicine (0.0625-0.5 mu mol/L) into each hole according to the concentration gradient of the concentration, wherein each concentration is provided with 3 parallel holes. The experiment was divided into drug test group (with different concentrations of test drug added), control group (with culture medium and cells only, without test drug added) and blank group (with culture medium only, without cells and test drug added). Placing the medicated hole plate at 37 deg.C and 5% CO2Culturing in an incubator for 24 h. The activity of the control drug was determined as per the method of the test sample. In the well plate after 48h incubation, 20uL of MTT (5 in PBS) was added to each wellg/L). After standing at 37 ℃ for 4h, the supernatant was removed. Add 150uL DMSO to each well, shake for 10min to dissolve the Formazan crystals. Finally, the absorbance of each well was measured at a wavelength of 570nm using a BioTek multifunctional microplate reader.
Data processing: data processing Using GraAr Pad Prism version5.0 program, Complex IC50Fitting was done by a non-linear regression model with sigmoidal dose response in the program.
Analyzing human lung cancer cell (A549) cell line, human cervical cancer cell (Hela) cell line and human gastric cancer cell (HGC-27) cell line by MTT analysis method, and determining IC50The results are shown in table 1, with the conclusion that: as can be seen from the data in the table, the tricyclohexyltin quinoxaline-2-formate complex disclosed by the invention is used as an anticancer drug, has high anticancer activity on human lung cancer, human cervical cancer and human gastric cancer, and can be used as a candidate complex of the anticancer drug.
Table 1 tricyclohexyltin quinoxaline-2-carboxylate complex anticancer drug in vitro activity test data.
| Human lung cancer cell | Human cervical cancer cell | Human gastric cancer cell | |
| Cell line | A549 | Hela | HGC-27 |
| IC50μM | 0.2314 | 0.1463 | 0.2467 |
The tricyclohexyltin quinoxaline-2-carboxylate complexes prepared in the remaining examples were tested for anticancer activities against human lung cancer cells (A549), human cervical cancer cells (Hela) and human gastric cancer cells (HGC-27) by MTT method in the same experimental examples, and the test results were substantially the same as those in Table 1.
Claims (7)
1. A tricyclohexyltin quinoxaline-2-carboxylate complex, which is a complex of the following structural formula (I):
(I)。
2. the quinoxaline-2-carboxylate complex containing tricyclohexyltin according to claim 1, having infrared spectral data: FT-IR (KBr, v/cm)-1) 3730.33(m), 2918.30(s), 2845.00(m), 2650.19(w),1633.71(s), 1490.97(m), 1444.68(m), 1365.60(s), 1325.10(m), 1247.94(w),1203.58(w), 1168.86(m), 1126.43(w), 1085.92(w), 1020.34(m), 993.34(m), 956.69(w), 802.39(m), 754.17(s), 680.87(m), 653.87(m), 599.86(m), 522.71(w), 491.85(w),418.55(m), and nuclear magnetic spectrum data thereof:1H NMR (CDCl3, 500 MHz)δ(ppm): 9.55(s, 1H), 8.32(d,J=8Hz, 1H), 8.15 (d,J=8Hz, 1H), 7.86-7.80 (m, 2H), 2.12-1.96 (m, 9H),1.81-1.64 (m, 15H), 1.43-1.35(m, 9H);13CNMR(CDCl3, 125MHz)δ(ppm):168.01,146.05, 144.88, 143.26, 141.92, 131.50, 130.81, 130.40, 129.11, 34.56, 31.15,28.93(t,J= 32 Hz), 26.84;119Sn NMR (CDCl3, 186 MHz),δ(ppm):38.38。
3. the preparation method of tricyclohexyl tin quinoxaline-2-formate complex as claimed in claim 1, wherein tricyclohexyl tin hydroxide, quinoxaline-2-carboxylic acid and solvent toluene are sequentially added into a 250 mL round bottom flask, a Dean-Stark water separator is arranged, and the reaction is performed at 112-120 ℃ under heating and reflux for 6-12 h; after the reaction is finished, filtering while the reaction is hot, removing the solvent from the filtrate by using a rotary evaporator to obtain a white solid, and recrystallizing the white solid by using ethanol to obtain the tricyclohexyl tin quinoxaline-2-formate complex.
4. The method according to claim 3, wherein the ratio of the amounts of tricyclohexyltin hydroxide and quinoxaline-2-carboxylic acid is 1 (1 to 1.1).
5. The method according to claim 3, wherein the solvent toluene is used in an amount of 25 to 35 ml per mmol of tricyclohexyltin hydroxide.
6. Use of the tricyclohexyltin quinoxaline-2-carboxylate complex according to claim 1 in the preparation of an anti-cancer medicament.
7. The use of claim 7, wherein the cancer cell is lung cancer, cervical cancer, gastric cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911366728.5A CN111138478B (en) | 2019-12-26 | 2019-12-26 | Tricyclohexyltin quinoxaline-2-formate complex, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911366728.5A CN111138478B (en) | 2019-12-26 | 2019-12-26 | Tricyclohexyltin quinoxaline-2-formate complex, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111138478A true CN111138478A (en) | 2020-05-12 |
| CN111138478B CN111138478B (en) | 2023-07-14 |
Family
ID=70520400
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911366728.5A Active CN111138478B (en) | 2019-12-26 | 2019-12-26 | Tricyclohexyltin quinoxaline-2-formate complex, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111138478B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101353357A (en) * | 2008-09-11 | 2009-01-28 | 聊城大学 | Organo-tin compound, preparation and use thereof |
-
2019
- 2019-12-26 CN CN201911366728.5A patent/CN111138478B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101353357A (en) * | 2008-09-11 | 2009-01-28 | 聊城大学 | Organo-tin compound, preparation and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| WENCHAO DING等，: "Synthesis, Characterization, and In Vitro Cytotoxicity of Triorganotin 3,5-Di-tert-butyl-4-hydroxybenzoates", 《SYNTHESIS AND REACTIVITY IN INORGANIC, METAL-ORGANIC,AND NANO-METAL CHEMISTRY》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111138478B (en) | 2023-07-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111116638A (en) | Tricyclohexyltin 3-methylthiophene-2-formate complex, and preparation method and application thereof | |
| CN111057092B (en) | Tris (2-methyl-2-phenylpropyl) tin 3-aminopyrazinate complex and preparation method and application thereof | |
| CN111138480B (en) | Preparation method and application of tricyclohexyltin quinoline-4-formate complex | |
| CN111138478A (en) | Tricyclohexyltin quinoxaline-2-formate complex and preparation method and application thereof | |
| CN111153929A (en) | Preparation method and application of tricyclohexyltin 4-chlorobenzoate complex | |
| CN111057094B (en) | Tris (2-methyl-2-phenylpropyl) tin benzothiophene-2-formate complex and preparation method and application thereof | |
| CN111138479B (en) | Tricyclohexyltin 3-methylbenzofuran-2-formate complex and preparation method and application thereof | |
| CN111057093A (en) | Tricyclohexyltin benzothiophene-2-formate complex and preparation method and application thereof | |
| CN111138483A (en) | Tricyclohexyltin 2-chlorothiophene-5-formate complex and preparation method and application thereof | |
| CN111138482A (en) | Tris (2-methyl-2-phenyl propyl) tin 5-bromo-2-furoate complex and preparation method and application thereof | |
| CN111138476B (en) | Tris (2-methyl-2-phenylpropyl) tin 2-chlorothiophene-5-formate complex and preparation method and application thereof | |
| CN111138474A (en) | Tricyclohexyltin 2-bromothiophene-5-formate complex and preparation method and application thereof | |
| CN111057095B (en) | Tricyclohexyltin 5-chloro-2-hydroxypyridine-3-formate complex and preparation method and application thereof | |
| CN111647014A (en) | Tricyclohexyltin 5-bromo-2-furoate complex and preparation method and application thereof | |
| CN111138475B (en) | Tris (2-methyl-2-phenylpropyl) tin 3-methylbenzofuran formate complex and preparation method and application thereof | |
| CN111153927A (en) | Bis [ tri (2-methyl-2-phenylpropyl) tin ]2, 3-pyrazine diformate and preparation method and application thereof | |
| CN111116636B (en) | Preparation method and application of tricyclohexyltin indole-6-formate complex | |
| CN111269260A (en) | Tri (2-methyl-2-phenylpropyl) tin 3-bromothiophene-2-formate complex and preparation method and application thereof | |
| CN111138473A (en) | Tris (2-methyl-2-phenylpropyl) tin 3-methyl-thiophene-2-formate and preparation method and application thereof | |
| CN111116641A (en) | Bis [ tri (2-methyl-2-phenyl) propyltin ] furan-2-formate complex and preparation method and application thereof | |
| CN111116637B (en) | Tris (2-methyl-2-phenylpropyl) stannquinoxaline-2-formate complex and preparation method and application thereof | |
| CN111138477B (en) | Preparation method and application of tricyclohexyltin quinoline-6-formate complex | |
| CN111217851B (en) | Preparation method and application of tricyclohexyltin indole-4-formate complex | |
| CN111138485B (en) | Preparation method and application of tricyclohexyl tin cinnamate complex | |
| CN111116640A (en) | Preparation method and application of tri (2-methyl-2-phenylpropyl) tin indole-6-formate complex |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20200512 Assignee: Hunan Hengfei Biopharmaceutical Co.,Ltd. Assignor: Hengyang Normal University Contract record no.: X2023980047818 Denomination of invention: A tricyclohexyltin quinoxaline-2-carboxylate complex and its preparation method and application Granted publication date: 20230714 License type: Common License Record date: 20231123 |