CN110698383B - Structure, synthesis and application of benzil hydrazone-3-acetyl indole - Google Patents
Structure, synthesis and application of benzil hydrazone-3-acetyl indole Download PDFInfo
- Publication number
- CN110698383B CN110698383B CN201911103494.5A CN201911103494A CN110698383B CN 110698383 B CN110698383 B CN 110698383B CN 201911103494 A CN201911103494 A CN 201911103494A CN 110698383 B CN110698383 B CN 110698383B
- Authority
- CN
- China
- Prior art keywords
- benzil
- crystal
- organic solvent
- schiff base
- acetyl indole
- 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.)
- Active
Links
- 230000015572 biosynthetic process Effects 0.000 title description 4
- 238000003786 synthesis reaction Methods 0.000 title description 4
- -1 benzil hydrazone-3-acetyl indole Chemical compound 0.000 title description 3
- VUIMBZIZZFSQEE-UHFFFAOYSA-N 1-(1h-indol-3-yl)ethanone Chemical compound C1=CC=C2C(C(=O)C)=CNC2=C1 VUIMBZIZZFSQEE-UHFFFAOYSA-N 0.000 claims abstract description 58
- 239000013078 crystal Substances 0.000 claims abstract description 31
- 239000002262 Schiff base Substances 0.000 claims abstract description 16
- 150000004753 Schiff bases Chemical class 0.000 claims abstract description 16
- ZWPOAAKGAFHAEX-HBKJEHTGSA-N (e)-[(2e)-2-hydrazinylidene-1,2-diphenylethylidene]hydrazine Chemical compound C=1C=CC=CC=1\C(=N/N)\C(=N\N)\C1=CC=CC=C1 ZWPOAAKGAFHAEX-HBKJEHTGSA-N 0.000 claims abstract description 8
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 6
- 201000005202 lung cancer Diseases 0.000 claims abstract description 6
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 6
- 238000002844 melting Methods 0.000 claims abstract description 6
- 230000008018 melting Effects 0.000 claims abstract description 6
- 241000588724 Escherichia coli Species 0.000 claims abstract description 5
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 4
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical compound C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 10
- 239000002994 raw material Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 238000003746 solid phase reaction Methods 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 6
- CDQPGWNBSOSEMZ-DTQAZKPQSA-N (2e)-2-hydrazinylidene-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(=N/N)\C(=O)C1=CC=CC=C1 CDQPGWNBSOSEMZ-DTQAZKPQSA-N 0.000 claims description 5
- 230000000844 anti-bacterial effect Effects 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- PQMPNCXALNJELA-UHFFFAOYSA-N 1-(1H-indol-3-yl)ethylidenehydrazine Chemical compound CC(=NN)c1c[nH]c2ccccc12 PQMPNCXALNJELA-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- RKTYLMNFRDHKIL-UHFFFAOYSA-N copper;5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Cu+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 RKTYLMNFRDHKIL-UHFFFAOYSA-N 0.000 claims description 2
- 238000001308 synthesis method Methods 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 3
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 239000002244 precipitate Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 abstract description 4
- 239000008204 material by function Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 description 8
- 238000010586 diagram Methods 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000002189 fluorescence spectrum Methods 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 239000000203 mixture 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
- 239000000376 reactant Substances 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
- 238000012360 testing method Methods 0.000 description 3
- 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
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000921 elemental analysis Methods 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
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 2
- CDQPGWNBSOSEMZ-UHFFFAOYSA-N 2-hydrazinylidene-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(=NN)C(=O)C1=CC=CC=C1 CDQPGWNBSOSEMZ-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000007605 air drying 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
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000003385 bacteriostatic effect Effects 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
- 201000011510 cancer Diseases 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
- 238000000576 coating method Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 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
- 239000012567 medical material Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012860 organic pigment Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research 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
- 238000010189 synthetic method Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
-
- 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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Indole Compounds (AREA)
Abstract
The invention relates to the field of medicinal chemistry and functional materials, in particular to two Schiff base crystals generated by benzildihydrazone or benzildihydrazone and 3-acetyl indole, wherein the former is double Schiff base, the appearance of the double Schiff base is yellow rod-shaped crystal, the melting point is 270.2-271.7 ℃, and the molecular formula is C 34 H 28 N 6 Molecular weight 520.62; the latter is Shan Xifu alkali, and has yellow needle crystal appearance, melting point of 223.1-224.4 deg.C, and molecular formula C 24 H 19 N 3 O, molecular weight 365.43; the structures of the two are as follows:
Description
The technical field is as follows:
the invention relates to the field of medicinal chemistry and functional materials, in particular to a structure of Schiff base generated by reaction of benzildizone or benzildizone and 3-acetyl indole, application of the structure in fluorescent materials, anticancer drugs and antibacterial drugs, and application of the structure in the fields of medical materials, functional materials and the like.
Background art:
schiff base is a compound containing an imine or azomethine group, of the general formula R 1 R 2 C＝NR 3 . 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, 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, laser and the like; therefore, the synthesis and property research of the novel Schiff base have great significance.
Disclosure of Invention
The invention relates to a method for synthesizing two types of Schiff bases which are reaction products of benzil hydrazone and 3-acetyl indole, wherein the reaction products of the benzil dihydrazone and the 3-acetyl indole are called benzil dihydrazone-N, N' -di (3-acetyl indole), and the reaction products of the benzil monohydrazone and the 3-acetyl indole are called benzil monohydrazone-N-3-acetyl indole; the former being a bisSchiff base, yellow rod-shaped crystal in appearance, melting point of 270.2-271.7 deg.C, molecular formula C 34 H 28 N 6 Molecular weight 520.62; the latter is Shan Xifu alkali, and has yellow needle crystal appearance, melting point of 223.1-224.4 deg.C, and molecular formula C 24 H 19 N 3 O, molecular weight 365.43; the structures of the two are as follows:
1. and (5) structure identification.
The elemental analysis of the benzil dihydrazone-N, N' -bis (3-acetyl indole) shows that the percentage content of C, H, N is respectively as follows: c78.49 (78.44), H5.47 (5.42), N16.21% (16.14%) (theoretical values in parentheses); the analysis of the single crystal structure shows that the crystal is a triclinic system, P-1 space group,
α＝64.941(4)°，β＝79.573(3)°，γ＝76.829(4)°，/>
z =2; in connection with 1 HNMR spectrum, 13 The CNMR spectra are shown in figure 1 and figure 2 respectively; the structure diagram and the stacking diagram of the single crystal structure are shown in the attached figures 3 and 4 respectively.
Elemental analysis of benzil monohydrazone-N-3-acetyl indole showed that the percentage content of C, H, N is C79.24 (78.88), H6.11 (5.24), N12.03% (11.50%) (theoretical in parentheses); the analysis of the single crystal structure shows that the crystal is tetragonal system, P4 3 2 1 2 the space group is formed by the space group,
α＝β＝γ＝90°，/>
z =8; to aIs/are as follows 1 HNMR spectrum, 13 The CNMR spectra are shown in figure 5 and figure 6 respectively; the structure diagram and the stacking diagram of the single crystal structure are shown in figures 7 and 8 respectively.
2. A synthetic method.
There are two methods for synthesizing benzildihydrazone-N, N' -bis (3-acetylindole): the first method takes benzil dihydrazone and 3-acetyl indole as raw materials and comprises the following steps:
1) Dissolving benzildihydrazone in a proper organic solvent, adding 3-acetyl indole according to a certain substance amount ratio, and stirring and reacting for a certain time at a certain temperature to complete the reaction; if solid phase reaction is adopted, organic solvent is not used, and the grinding reaction of the two can be finished for a certain time.
2) Filtering, and naturally volatilizing the filtrate to precipitate yellow rod-shaped crystals which are target products; if solid phase reaction is adopted, the target product crystal can be obtained by recrystallization with proper organic solvent after the reaction is finished.
The second method takes diphenylethanedione and 3-acetyl indole hydrazone as raw materials, and is completed in one step in a proper organic solvent, and the steps are as follows:
1) Dissolving diphenylethanedione in a proper organic solvent, adding 3-acetyl indole 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 solid phase reaction is adopted, organic solvent is not used, and the grinding reaction of the two can be finished for a certain time.
2) Filtering, and naturally volatilizing the filtrate to precipitate yellow rod-shaped crystals which are target products; if solid phase reaction is adopted, the target product crystal can be obtained by recrystallization with proper organic solvent after the reaction is finished.
The difference of the two preparation methods is mainly that the reactants are different, but the molar ratio of the reaction raw materials is between 4:1 and 1:4.
The synthesis of the benzil monohydrazone-N-3-acetyl indole takes the benzil monohydrazone and the 3-acetyl indole as raw materials, other steps are the same as the synthesis method of the benzil dihydrazone-N, N' -di (3-acetyl indole), and the molar ratio of reactants is between 4:1 and 1:4.
The organic solvent (solvent for reaction or solvent for recrystallization) in the above two preparation methods is selected from: methanol, ethanol, acetonitrile, dichloromethane, chloroform, tetrahydrofuran, acetone, etc.; in the solid-phase reaction, organic solvents are not used, and raw materials can be directly reacted.
Preferably, the reaction temperature is normal temperature or heating reflux, and the reaction method is stirring or grinding.
Preferably, the reaction time is selected from: 0.5-10h.
The beneficial effects of the invention are: can synthesize more complex functional molecular materials by simpler steps and reactants.
3. In vitro antitumor activity:
human lung cancer cells A549 or mouse breast cancer cells 4T growing in logarithmic phase 1 The cells were digested with 0.25% trypsin to give single cells, which were then prepared in a concentration of 1.25X 10 using a culture solution of F12K containing 10% fetal bovine serum 7 One cell/L suspension of single cells, cells were seeded in 96-well plates at 200. Mu.L per well (2.5X 10 per well) 3 Individual cells). Place 96-well cell culture plates in CO 2 In an incubator, 5% CO at 37% 2 Culturing 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 96h.
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 calculated according to the following formula:
cell inhibition% = (control OD value-experimental OD value)/control OD value × 100%
The test result shows that the benzil dihydrazone-N, N' -di (3-acetyl indole) is used for treating human lung cancer cell A549 and mouse breast cancer cell 4T 1 Has IC50 (half inhibitory concentration of the drug) of 8.5. Mu.M and 7.0Mu M; benzoylmonohydrazone-N-3-acetylindole as human lung cancer cell A549 and mouse breast cancer cell 4T 1 IC50 of (a) are 43.0. Mu.M and 30.0. Mu.M, respectively; this indicates that the two Schiff base molecules have good inhibitory effects on two cancer cells; compared with the cisplatin, the dicsfungine has better effect, and has better effect than the cisplatin in human lung cancer cells A549 and mouse breast cancer cells 4T 1 Inhibitory Effect (IC) 50 6.5 and 0.5 μ M, respectively).
4. Antibacterial activity:
the antibacterial effect is measured by adopting a filter paper diffusion method: circular filter paper sheets (each sheet absorbs 10 microliters of liquid medicine) with the same size and the same diameter and 8mm are immersed in DMSO solution of a to-be-detected medicine with the concentration of 100 mug/mL, the filter paper sheets are taken out after 30 minutes, air drying is carried out, the medicine carrying capacity of each filter paper sheet is about 1 mug, then the filter paper sheets are placed in the center of a flat plate coated with escherichia coli or staphylococcus aureus, a label is pasted on a culture dish cover, the culture dish is marked, the diameter of an antibacterial ring is measured by a vernier caliper after the culture dish is placed in a constant temperature incubator and is cultured for 24 hours at 37 ℃, and the diameter of the antibacterial ring is compared with that of penicillin potassium (the concentration of 10 mug/mL).
Test results show that the diameters of inhibition zones of the benzil dihydrazone-N, N' -bis (3-acetyl indole) to escherichia coli/staphylococcus aureus are 8.1 mm and 9.0mm respectively, and the diameters of inhibition zones of the benzil monohydrazone-N-3-acetyl indole to the escherichia coli/staphylococcus aureus are 8.2 mm and 9.5mm respectively; both are smaller than 29.0 and 28.4mm for potassium penicillin, but still have some bacteriostatic activity.
5. Ultraviolet and fluorescent properties
The benzil dihydrazone-N, N' -di (3-acetyl indole) has three strong absorption peaks near 210nm, 258nm and 340nm, and the ultraviolet spectrum is shown in figure 9; has strong fluorescence emission peak in the range of 300-400nm and a medium intensity fluorescence emission peak in the range of 420-500nm, and the fluorescence spectrum is shown in figure 10.
The benzil monohydrazone-N-3-acetyl indole has four strong absorption peaks near 203nm, 217nm, 251nm and 353nm, and the ultraviolet spectrum is shown in figure 11; has strong fluorescence emission peak in the range of 300-375nm, and the fluorescence spectrum is shown in figure 12.
The test results show that the two compounds have good fluorescence properties and can be used as fluorescent materials.
Detailed Description
In order to better understand the present invention, the following embodiment further illustrates the technical solution of the present invention.
Example 1.
0.238g of benzil dihydrazone is dissolved in 30ml of acetonitrile, 0.318g of 3-acetyl indole is added according to the mass proportion of 1:2, the mixture is heated and refluxed for 10 hours, and after the solvent is volatilized to leave about 5ml, a yellow rod-shaped crystal, namely benzil dihydrazone-N, N' -bis (3-acetyl indole), can be recrystallized by methanol to obtain a purer product.
Example 2.
0.224g of benzil monohydrazone is dissolved in 30ml of acetonitrile, 0.159g of 3-acetyl indole is added according to the mass proportion of 1:1, the mixture is heated and refluxed for 3 hours, and yellow needle-shaped crystals, namely the benzil monohydrazone-N-3-acetyl indole, can be obtained after the solvent is volatilized to about 5ml, and can be recrystallized by methanol to obtain a purer product.
Drawings
FIG. 1 is a drawing showing the preparation of benzildihydrazone-N, N' -bis (3-acetylindole) 1 H NMR spectrum (solvent DMSO-d 6).
FIG. 2 is a drawing showing the preparation of benzildihydrazone-N, N' -bis (3-acetylindole) 13 CNMR spectrum (solvent DMSO-d 6).
FIG. 3 is a crystal structure diagram of benzildihydrazone-N, N' -bis (3-acetylindole) with an ellipsoid probability of 30%.
FIG. 4 is a packing diagram of the crystal structure of benzildihydrazone-N, N' -bis (3-acetylindole) with 10% probability of ellipsoid.
FIG. 5 shows the preparation of benzil monohydrazone-N-3-acetyl indole 1 H NMR spectrum (solvent DMSO-d 6).
FIG. 6 shows the preparation of benzil monohydrazone-N-3-acetyl indole 13 CNMR spectrum (solvent DMSO-d 6).
FIG. 7 shows the crystal structure of benzil monohydrazone-N-3-acetyl indole with 30% probability of ellipsoid.
FIG. 8 is a crystal structure stacking diagram of benzil monohydrazone-N-3-acetylindole with 10% probability of ellipsoid.
FIG. 9 is a UV-VIS spectrum of benzildihydrazone-N, N' -bis (3-acetylindole) (10) -5 M ethanol solution).
FIG. 10 is a fluorescent spectrum of benzildihydrazone-N, N' -bis (3-acetylindole) (10) -5 M ethanol solution).
FIG. 11 is a UV-VIS spectrum of benzil monohydrazone-N-3-acetylindole (10) -5 M ethanol solution).
FIG. 12 shows the fluorescence spectrum of benzil monohydrazone-N-3-acetylindole (10) -5 M ethanol solution).
Claims (5)
1. Two Schiff base crystals are generated by benzildihydrazone or benzil monohydrazone and 3-acetyl indole, the former is double Schiff base, the appearance is yellow rod-shaped crystal, the melting point is 270.2-271.7 ℃, and the molecular formula C 34 H 28 N 6 Molecular weight 520.62; the latter is Shan Xifu alkali, and has yellow needle crystal appearance, melting point of 223.1-224.4 deg.C, and molecular formula C 24 H 19 N 3 O, molecular weight 365.43; the structures of the two are as follows:
the double schiff base is crystallized as a triclinic system, P-1 space group, a =10.2585 (4) A, b =11.9610 (5) A, c = 12.8232 (6) A, α = 64.941 (4) DEG, β = 79.573 (3) DEG, γ =76.829 (4) DEG, V = 1381.45 (11) A 3 Z =2; shan Xifu alkali crystallization is tetragonal system, P4 3 2 1 2 space group, a = b = 8.3580 (1), c = 54.6705 (7), a = β = γ =90 °, V = 3819.07 (10) a 3 ，Z=8。
2. The two synthesis methods of the benzildihydrazone-N, N' -bis (3-acetylindole) crystal as claimed in claim 1, wherein the first method is to use benzildihydrazone and 3-acetylindole as raw materials, dissolve the two raw materials in methanol, ethanol, acetonitrile, dichloromethane, chloroform, tetrahydrofuran or acetone organic solvent respectively, mix them according to the ratio of 4:1-1:4 substance, stir and react for 0.5-10h at normal temperature or under heating reflux, filter, evaporate the filtrate naturally, and precipitate yellow rod-shaped crystal as the target product; or solid phase reaction is adopted, organic solvent is not used, the two raw materials are mixed and ground for reaction for 0.5 to 10 hours according to the mass ratio of 4:1 to 1:4, and then methanol, ethanol, acetonitrile, dichloromethane, chloroform, tetrahydrofuran or acetone organic solvent is used for recrystallization to obtain target product crystals; the second method takes diphenylethanedione and 3-acetyl indole hydrazone as raw materials, and the steps are the same as the first method.
3. The method for synthesizing the benzil monohydrazone-N-3-acetylindole crystal as claimed in claim 1, dissolving the benzil monohydrazone and the 3-acetylindole in methanol, ethanol, acetonitrile, dichloromethane, chloroform, tetrahydrofuran or acetone organic solvent respectively, mixing according to the ratio of the amount of 4:1-1:4 substance, stirring and reacting for 0.5-10h at normal temperature or under heating reflux, filtering, and naturally volatilizing the filtrate to precipitate a yellow needle crystal which is the target product; or solid phase reaction is adopted, organic solvent is not used, the two raw materials are mixed and ground for reaction for 0.5 to 10 hours according to the mass ratio of 4:1 to 1:4, and then methanol, ethanol, acetonitrile, dichloromethane, chloroform, tetrahydrofuran or acetone organic solvent is used for recrystallization to obtain the target product crystal.
4. The use of two compounds according to claim 1 or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the prevention and/or treatment of tumors, wherein: the tumor for inhibiting the benzil dihydrazone-N, N' -bis (3-acetyl indole) or the pharmaceutically acceptable salt thereof is breast cancer, and the tumor for inhibiting the benzil monohydrazone-N-3-acetyl indole or the pharmaceutically acceptable salt thereof is lung cancer or breast cancer.
5. Use of two compounds as claimed in claim 1 for the preparation of an antibacterial medicament or material, which is effective in inhibiting the proliferation of escherichia coli and staphylococcus aureus.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911103494.5A CN110698383B (en) | 2019-11-13 | 2019-11-13 | Structure, synthesis and application of benzil hydrazone-3-acetyl indole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911103494.5A CN110698383B (en) | 2019-11-13 | 2019-11-13 | Structure, synthesis and application of benzil hydrazone-3-acetyl indole |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110698383A CN110698383A (en) | 2020-01-17 |
| CN110698383B true CN110698383B (en) | 2023-03-24 |
Family
ID=69205038
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911103494.5A Active CN110698383B (en) | 2019-11-13 | 2019-11-13 | Structure, synthesis and application of benzil hydrazone-3-acetyl indole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110698383B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113694064A (en) * | 2021-09-17 | 2021-11-26 | 齐鲁工业大学 | Application of bispyridone hydrazone-3-indole formaldehyde Schiff base |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945302A (en) * | 2015-06-12 | 2015-09-30 | 齐鲁工业大学 | Structure, preparation and application of benzil dihydrazone-indole-3-carboxaldehyde dual-Schiff base |
-
2019
- 2019-11-13 CN CN201911103494.5A patent/CN110698383B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945302A (en) * | 2015-06-12 | 2015-09-30 | 齐鲁工业大学 | Structure, preparation and application of benzil dihydrazone-indole-3-carboxaldehyde dual-Schiff base |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110698383A (en) | 2020-01-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104945302B (en) | The structure of the double Schiff bases of 3 indolecarboxaldehyde of benzil dihydrazone, preparation and use | |
| 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 | |
| CN110698383B (en) | Structure, synthesis and application of benzil hydrazone-3-acetyl indole | |
| CN110606843B (en) | Structure, preparation and application of bipyridyl ketone hydrazone-2-acetylpyrazine | |
| CN107043345B (en) | 4-acetylbiphenyl hydrazone-indoline -2,3- diketone Schiff base preparation, structure and purposes | |
| CN110698382B (en) | Application of benzil hydrazone-3-indole formaldehyde Schiff base | |
| CN109912491B (en) | Preparation and application of 4-hydroxybenzophenone hydrazone-isatin Schiff base | |
| CN110590765B (en) | Structure, preparation and application of 2-thiazole formaldehyde-furfural Schiff base | |
| CN109824572B (en) | Structure, preparation and application of 4-hydroxybenzophenone hydrazone-1-methyl-3 indole formaldehyde Schiff base | |
| CN107266349A (en) | Preparation, structure and the purposes of the indolecarboxaldehyde Schiff base of 4-acetylbiphenyl hydrazone 2 | |
| CN105348146A (en) | Structure, preparation and use of benzil hydrazone-chlorobenzaldehyde bis-Schiff base | |
| CN109912517B (en) | Preparation and application of 4-hydroxybenzophenone hydrazone-2-acetylpyrazine Schiff base | |
| CN110577521B (en) | Structure, preparation and application of 2-thiazole formaldehyde-2-pyridine Schiff base | |
| CN109824541B (en) | Preparation and use of (1Z, 2Z) -1, 2-bis ((2-fluorophenyl) (4-fluorophenyl) methylene) hydrazine | |
| CN110590764B (en) | Structure, preparation and application of 2-thiazole formaldehyde-4-pyridine Schiff base | |
| CN110590763B (en) | Structure, preparation and application of 2-thiazole formaldehyde-thiophene Schiff base | |
| CN110563667B (en) | Structure, preparation and application of 2-thiazole formaldehyde-1-naphthalene Schiff base | |
| CN113577071A (en) | Application of bispyridone hydrazone-2-indole formaldehyde Schiff base | |
| CN105367445B (en) | Preparation, structure and application of benzyl dihydrazone-N-mono-(2-hydroxy-4-diethylin-1-formyl benzene) | |
| CN110563716B (en) | Structure, preparation and application of 2-thiazole formaldehyde-6-indole Schiff base | |
| CN109912451B (en) | Preparation and application of 4-hydroxybenzophenone hydrazone-salicylaldehyde Schiff base | |
| CN110590697B (en) | Structure, preparation and application of 2-thiazole formaldehyde-benzene Schiff base | |
| CN113730405A (en) | Application of bispyridone hydrazone-4-indole formaldehyde 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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 250353 Qilu University of technology, Changqing University Town, Jinan City, Shandong Province Patentee after: Qilu University of Technology (Shandong Academy of Sciences) Country or region after: China Address before: 250353 Qilu University of technology, Changqing University Town, Jinan City, Shandong Province Patentee before: Qilu University of Technology Country or region before: China |