CN113694064A - Application of bispyridone hydrazone-3-indole formaldehyde Schiff base - Google Patents
Application of bispyridone hydrazone-3-indole formaldehyde Schiff base Download PDFInfo
- Publication number
- CN113694064A CN113694064A CN202111090352.7A CN202111090352A CN113694064A CN 113694064 A CN113694064 A CN 113694064A CN 202111090352 A CN202111090352 A CN 202111090352A CN 113694064 A CN113694064 A CN 113694064A
- Authority
- CN
- China
- Prior art keywords
- hydrazone
- schiff base
- indole
- reaction
- bispyridone
- 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.)
- Pending
Links
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 239000002262 Schiff base Substances 0.000 title claims abstract description 24
- 239000000843 powder Substances 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 5
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 5
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 4
- 241000588724 Escherichia coli Species 0.000 claims abstract description 4
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 4
- 239000000463 material Substances 0.000 claims abstract description 4
- 201000007270 liver cancer Diseases 0.000 claims abstract description 3
- 208000014018 liver neoplasm Diseases 0.000 claims abstract description 3
- 238000002844 melting Methods 0.000 claims abstract description 3
- 230000008018 melting Effects 0.000 claims abstract description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- UWDHESVDMJZCAI-UHFFFAOYSA-N 2-pyridin-2-yl-4h-pyridin-3-one Chemical compound O=C1CC=CN=C1C1=CC=CC=N1 UWDHESVDMJZCAI-UHFFFAOYSA-N 0.000 claims description 3
- 230000035755 proliferation Effects 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 20
- 150000004753 Schiff bases Chemical class 0.000 abstract description 13
- -1 bipyridone hydrazone Chemical class 0.000 abstract description 10
- 150000007857 hydrazones Chemical class 0.000 abstract description 8
- 230000005764 inhibitory process Effects 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 4
- 229940124350 antibacterial drug Drugs 0.000 abstract description 2
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 abstract description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract 1
- 230000009897 systematic effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 7
- 238000003746 solid phase reaction Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 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 3
- 238000001228 spectrum Methods 0.000 description 3
- OTYGWWHMSJZFID-UHFFFAOYSA-N 1H-indol-3-ylmethylidenehydrazine Chemical compound C1=CC=C2C(C=NN)=CNC2=C1 OTYGWWHMSJZFID-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 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
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- IDBOAVAEGRJRIZ-UHFFFAOYSA-N methylidenehydrazine Chemical compound NN=C IDBOAVAEGRJRIZ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 230000005918 in vitro anti-tumor Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012860 organic pigment Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Environmental Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Dentistry (AREA)
- Plant Pathology (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Wood Science & Technology (AREA)
- Epidemiology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the field of medicinal chemistry, in particular to application of Schiff base generated by reaction of bispyridone hydrazone and 3-indole formaldehyde in anticancer drugs, antibacterial drugs or antibacterial materials. Schiff base generated by reaction of bipyridone hydrazone and 3-indole formaldehyde, and systematic name is: 3- ((di (pyridin-2-yl) methylene) hydrazone) methyl) -1H-indole with the molecular formula C20H15N5(ii) a The appearance of the Schiff base is yellow powder, and the melting point is 166.7-168.3 ℃; the structure is as follows:
. The compound can be used for treating mouse breast cancer cell 4T1The IC50 (half inhibition concentration of the drug) is 11.5 mu M, the IC50 of human liver cancer Hep G2 cells is 13.0 mu M, and the drug has good tumor inhibition activity; and can effectively inhibit the propagation of escherichia coli and staphylococcus aureus.
Description
Technical Field
The invention relates to the field of medicinal chemistry, in particular to application of Schiff base generated by reaction of bispyridone hydrazone and 3-indole formaldehyde in anticancer drugs, antibacterial drugs or antibacterial materials.
Background
Schiff base is a compound containing an imine or azomethine group, of the general formula R1R2C=NR3. The Schiff base ligand with various structures and functions can be synthesized by introducing different substituent groups through the reaction design of a compound of an active carbonyl group and different amine compounds. Schiff base has many well-known obvious biological activities, such as antibiosis, antifungal, weeding, antituberculosis, anti-HIV, anticancer and the like, which makes it widely used in the fields of medicinal chemistry, functional materials and the like. In addition, the Schiff base with a large conjugated system often has good fluorescence property, and is widely applied to the fields of organic pigments, optical brighteners, photo-oxidizers, coatings, chemical and biochemical analysis, solar collectors, anti-counterfeiting marks, drug tracing, lasers and the like.
Disclosure of Invention
The invention relates to a synthetic method of Schiff base, namely the Schiff base generated by the reaction of bispyridone hydrazone and 3-indole formaldehyde, which is systematically named as follows: 3- ((di (pyridin-2-yl) methylene) hydrazone) methyl) -1H-indole with the molecular formula C20H15N5(ii) a The appearance of the Schiff base is yellow powder, and the melting point is 166.7-168.3 ℃; the structure is as follows.
And (5) structure identification.
The elemental analysis of the bipyridone hydrazone-3-indole carbaldehyde Schiff base showed that the C, H, N percentage content was 73.81%, 4.68% and 21.55% (theoretical value is respectively)73.83%, 4.65% and 21.52%), molecular weight 325.375; in connection with1HNMR spectrum,13The CNMR spectra are shown in figure 1 and figure 2 respectively.
A synthetic method.
The bipyridyl ketone hydrazone-3-indole formaldehyde Schiff base has two synthesis methods: the first method takes bipyridone hydrazone and 3-indole formaldehyde as raw materials and comprises the following steps.
1) Dissolving the dipyridone hydrazone in a proper organic solvent, adding the 3-indole formaldehyde according to a certain substance amount ratio, and stirring and reacting for a certain time at a certain temperature to complete the preparation.
The first step can also adopt solid phase reaction, namely organic solvent is not used, the dipyridone hydrazone and the 3-indole formaldehyde are mixed according to a certain substance amount ratio and then are ground and reacted for a certain time at normal temperature, and the obtained solid is the crude product of the target product.
2) If liquid phase reaction is adopted, filtering is carried out after the reaction is finished, and yellow powder separated out is a target product after the filtrate is naturally volatilized; if solid phase reaction is adopted, the target product can be obtained by recrystallization with proper organic solvent after the reaction is finished.
The second method takes the bipyridone and the 3-indole formaldehyde hydrazone as raw materials, and is completed in one step in a proper organic solvent, and the steps are as follows.
1) Dissolving dipyridone in a proper organic solvent, adding 3-indole formaldehyde hydrazone according to a certain substance amount ratio, and stirring and reacting at a certain temperature for a certain time to complete the reaction; if the solid-phase reaction is adopted, an organic solvent is not used, the two are mixed according to a certain proportion and then the grinding reaction is carried out for a certain time, and the obtained solid is the crude product of the target product.
2) If liquid phase reaction is adopted, filtering is carried out after the reaction is finished, and yellow powder separated out is a target product after the filtrate is naturally volatilized; if solid phase reaction is adopted, the target product can be obtained by recrystallization with proper organic solvent after the reaction is finished.
The two preparation methods are different mainly in reactants, but the molar ratio of the reaction raw materials is between 4:1 and 1: 4.
The organic solvent (including the solvent for reaction or the solvent for recrystallization) in the above two preparation methods is selected from: methanol, ethanol, acetonitrile, dichloromethane, chloroform, tetrahydrofuran, acetone, ethyl acetate, toluene, dioxane, etc.; the solid phase reaction does not use organic solvent, the raw materials react directly, and the solvent used for recrystallization can also be selected from the above solvents.
Preferably, the reaction temperature of the liquid phase reaction is normal temperature or heating reflux, and the reaction method is stirring; the solid phase reaction can be carried out at normal temperature, and the reaction method is grinding.
Preferably, the reaction time is selected from: 0.5-10 h.
The invention has the beneficial effects that: can synthesize more complex functional molecular materials by simpler steps and reactants.
In vitro antitumor activity.
Mice growing in log phase were breast cancer 4T1The cells or human hepatoma Hep G2 cells were digested with 0.25% pancreatic enzyme to become single cells, and prepared into 1.25X 10 by using 10% fetal bovine serum-containing F12K culture medium7One cell/L suspension of single cells, cells were seeded in 96-well plates at 200. mu.L per well (2.5X 10 per well)3Individual cells). Place 96-well cell culture plates in CO2In an incubator at 37 ℃ with 5% CO2Culturing for 48h under the condition.
When the cells in the wells are full (90% full), adding different doses of Schiff's base solution (200. mu.L/well) according to experimental groups to make the final concentrations of the compounds to be tested respectively 5. mu.M, 10. mu.M, 30. mu.M, 50. mu.M and 100. mu.M, setting 3 multiple wells in each group, and culturing for 96 h.
mu.L of MTT at a concentration of 0.5g/L was added to each well, and the culture was continued for 4 hours to reduce MTT to Formazan (Formazan). After all the supernatants were aspirated, 200. mu.L of DMSO was added to each well, and the mixture was shaken for 15min to dissolve formazan sufficiently, and then absorbance (OD value) at 490nm was measured using an ELISA detector. Then, the calculation was performed as follows.
Cell inhibition% = (control OD value-experimental OD value)/control OD value × 100%.
TestingThe result shows that the dipyridone hydrazone-3-indole formaldehyde Schiff base is applied to 4T of mouse breast cancer cells1IC50 (half maximal inhibitory concentration of drug) of 11.5 μ M; IC50 of Hep G2 cell of human liver cancer is 13.0 μ M; the inhibition rate of human foreskin fibroblast HFF-1 is 98.2 mu M; this indicates that the Schiff base molecule has a very good inhibitory effect on both cancer cells, and an inhibitory effect (IC) of cisplatin on both cancer cells50=5.5 μ M and 4.9 μ M) and has a low inhibition rate on normal cells.
And (4) bacteriostatic activity.
The antibacterial effect is measured by adopting a filter paper diffusion method: soaking circular filter paper sheets (each sheet absorbs 10 microliters of liquid medicine) with the same size and the same diameter of 8mm into DMSO (dimethylsulfoxide) solution of a to-be-detected medicine with the concentration of 100 mug/mL, taking out the filter paper sheets after 30 minutes, airing, wherein the drug-loading capacity of each filter paper sheet is about 1 mug, then placing the filter paper sheets into the center of a plate coated with escherichia coli or staphylococcus aureus, pasting a label on a culture dish cover, marking, placing the culture dish into a constant-temperature incubator, culturing for 24 hours at 37 ℃, measuring the diameter of an antibacterial ring by using a vernier caliper, and comparing with penicillin potassium (the concentration of 10 mug/mL).
Test results show that the diameters of inhibition zones of the bispyridone hydrazone-3-indole formaldehyde Schiff base on escherichia coli/staphylococcus aureus are 13.1 mm and 12.6mm respectively; although smaller than 29.0 and 28.4mm of penicillin potassium, still has certain bacteriostatic activity.
Detailed Description
In order to better understand the present invention, the following embodiment further illustrates the technical solution of the present invention.
Example 1.
Weighing 1.98g (0.01 mol) of bispyridone hydrazone powder, placing the powder in a 100mL single-neck flask, pouring 30mL of toluene into the flask, stirring and dissolving at 50 ℃, weighing 1.45g (0.01 mol) of 3-indolylaldehyde after the toluene is completely dissolved, adding the mixture into the flask, heating to 80 ℃, refluxing and stirring for reaction for 8 hours, cooling to room temperature, filtering, placing the filtrate in a beaker for natural volatilization, and obtaining yellow powder at the bottom of the beaker after about 1 week, namely the bispyridone hydrazone-3-indolylaldehyde Schiff base which can be recrystallized by methanol to obtain a purer product.
Example 2.
Dissolving 1.84g (0.01 mol) of bipyridyl ketone in 30ml of ethyl acetate, adding 1.59g of 3-indolylformaldehyde hydrazone according to the mass ratio of 1:1, heating and refluxing for 3h, cooling to room temperature, filtering, placing the filtrate in a beaker for natural volatilization, and obtaining yellow powder after the solvent is volatilized to the residual about 5ml, namely bipyridyl ketone hydrazone-3-indolylformaldehyde Schiff base, and recrystallizing with methanol to obtain a purer product.
Example 3.
1.84g (0.01 mol) of bipyridyl ketone and 1.59g (0.01 mol) of 3-indole carbaldehyde hydrazone are mixed and ground for 8 hours to obtain yellow powder, namely bipyridyl ketone hydrazone-3-indole carbaldehyde Schiff base, and ethyl acetate can be used for recrystallization to obtain a purer product.
Drawings
FIG. 1 shows the preparation of bispyridone hydrazone-3-indolecarboxaldehyde Schiff base1H NMR spectrum (solvent DMSO-d 6).
FIG. 2 shows the preparation of bispyridone hydrazone-3-indolecarboxaldehyde Schiff base13CNMR spectrum (solvent DMSO-d 6).
Claims (2)
1. The application of the compound shown as the following or pharmaceutically acceptable salt thereof in preparing the medicine for preventing and/or treating tumors is characterized in that: the tumor is breast cancer or liver cancer; the appearance of the bipyridone hydrazone-3-indole formaldehyde Schiff base is yellow powder, the melting point is 166.7-168.3 ℃, and the molecular formula is C20H15N5The structure is as follows:
2. use of a compound as claimed in claim 1 in an antibacterial medicament or material, which is effective in inhibiting the proliferation of escherichia coli or staphylococcus aureus.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111090352.7A CN113694064A (en) | 2021-09-17 | 2021-09-17 | Application of bispyridone hydrazone-3-indole formaldehyde Schiff base |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111090352.7A CN113694064A (en) | 2021-09-17 | 2021-09-17 | Application of bispyridone hydrazone-3-indole formaldehyde Schiff base |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113694064A true CN113694064A (en) | 2021-11-26 |
Family
ID=78661469
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111090352.7A Pending CN113694064A (en) | 2021-09-17 | 2021-09-17 | Application of bispyridone hydrazone-3-indole formaldehyde Schiff base |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113694064A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107266348A (en) * | 2017-06-20 | 2017-10-20 | 齐鲁工业大学 | Preparation, structure and the purposes of the indolecarboxaldehyde Schiff base of 4-acetylbiphenyl hydrazone 3 |
| CN110698383A (en) * | 2019-11-13 | 2020-01-17 | 齐鲁工业大学 | Structure, synthesis and application of benzil hydrazone-3-acetyl indole |
-
2021
- 2021-09-17 CN CN202111090352.7A patent/CN113694064A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107266348A (en) * | 2017-06-20 | 2017-10-20 | 齐鲁工业大学 | Preparation, structure and the purposes of the indolecarboxaldehyde Schiff base of 4-acetylbiphenyl hydrazone 3 |
| CN110698383A (en) * | 2019-11-13 | 2020-01-17 | 齐鲁工业大学 | Structure, synthesis and application of benzil hydrazone-3-acetyl indole |
Non-Patent Citations (1)
| Title |
|---|
| 王迪: "双（2-吡啶）酮腙席夫碱及其金属配合物的合成、结构与性质研究", 中国优秀硕士学位论文全文数据库 工程科技I辑, no. 2, pages 014 - 416 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110772506B (en) | Application of benzil hydrazone-1-naphthaldehyde Schiff base | |
| CN107266348B (en) | Preparation, structure and the purposes of 4-acetylbiphenyl hydrazone -3- indolecarboxaldehyde Schiff base | |
| CN110790695B (en) | Synthesis and application of benzil hydrazone-N-methyl-3-indole formaldehyde | |
| CN110606843B (en) | Structure, preparation and application of bipyridyl ketone hydrazone-2-acetylpyrazine | |
| CN107043345A (en) | Preparation, structure and the purposes of the diketone Schiff base of 4-acetylbiphenyl hydrazone indoline 2,3 | |
| CN110698383B (en) | Structure, synthesis and application of benzil hydrazone-3-acetyl indole | |
| CN113694064A (en) | Application of bispyridone hydrazone-3-indole formaldehyde Schiff base | |
| CN113730406A (en) | Application of bispyridone hydrazone-6-indole formaldehyde Schiff base | |
| CN113730405A (en) | Application of bispyridone hydrazone-4-indole formaldehyde Schiff base | |
| CN113577071A (en) | Application of bispyridone hydrazone-2-indole formaldehyde Schiff base | |
| CN110698382B (en) | Application of benzil hydrazone-3-indole formaldehyde Schiff base | |
| CN107266349B (en) | Preparation, structure and the purposes of 4-acetylbiphenyl hydrazone -2- indolecarboxaldehyde Schiff base | |
| CN110590765B (en) | Structure, preparation and application of 2-thiazole formaldehyde-furfural Schiff base | |
| CN109912491B (en) | Preparation and application of 4-hydroxybenzophenone hydrazone-isatin Schiff base | |
| CN109824572B (en) | Structure, preparation and application of 4-hydroxybenzophenone hydrazone-1-methyl-3 indole formaldehyde Schiff base | |
| CN113855673A (en) | Application of bispyridone hydrazone-N-methyl-3-indole formaldehyde Schiff base | |
| CN110590763B (en) | Structure, preparation and application of 2-thiazole formaldehyde-thiophene Schiff base | |
| CN110563716B (en) | Structure, preparation and application of 2-thiazole formaldehyde-6-indole Schiff base | |
| CN110577521B (en) | Structure, preparation and application of 2-thiazole formaldehyde-2-pyridine Schiff base | |
| CN105348146A (en) | Structure, preparation and use of benzil hydrazone-chlorobenzaldehyde bis-Schiff base | |
| CN109824541B (en) | Preparation and use of (1Z, 2Z) -1, 2-bis ((2-fluorophenyl) (4-fluorophenyl) methylene) hydrazine | |
| CN109912451B (en) | Preparation and application of 4-hydroxybenzophenone hydrazone-salicylaldehyde Schiff base | |
| CN110590764B (en) | Structure, preparation and application of 2-thiazole formaldehyde-4-pyridine Schiff base | |
| CN110590697B (en) | Structure, preparation and application of 2-thiazole formaldehyde-benzene Schiff base | |
| CN110563667B (en) | Structure, preparation and application of 2-thiazole formaldehyde-1-naphthalene Schiff base |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211126 |
|
| RJ01 | Rejection of invention patent application after publication |