CN117003759A - TB-pyridine cyano vinyl derivative with viscosity response and synthesis and application thereof - Google Patents

TB-pyridine cyano vinyl derivative with viscosity response and synthesis and application thereof Download PDF

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CN117003759A
CN117003759A CN202310984557.2A CN202310984557A CN117003759A CN 117003759 A CN117003759 A CN 117003759A CN 202310984557 A CN202310984557 A CN 202310984557A CN 117003759 A CN117003759 A CN 117003759A
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derivative
viscosity
cells
pyridine
endoplasmic reticulum
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苑睿
梁燕妮
庄敏艳
宛瑜
张鹏
吴翚
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Abstract

The invention provides a TB-pyridine cyano vinyl derivative with viscosity response, synthesis and application thereof, which is prepared by taking p-bromoaniline, paraformaldehyde, n-butyllithium, 4-pyridine acetyl nitrile and the like as raw materials through multi-step reaction. The structural formula of the derivative is shown as a derivative (6) of the following formula:the product has larger Stokes shift (207 nm) in the solution; has remarkable AIE properties; compared with the pure methanol, the fluorescence of 3 is enhanced by 5.3 times when methanol/glycerol=1/9 (v/v), the fluorescent probe has better response capability to viscosity and is easy to enter into living A549 cells, has stronger targeting capability to endoplasmic reticulum (pearson coefficient Pr=0.75), and has the potential of becoming an AIE endoplasmic reticulum viscosity response fluorescent probe; the inhibition capability of HpeG2 cells under dark and light conditions (428 nm) is strong, which indicates that the HpeG2 cells have the potential of developing into anti-liver cancer drugs.

Description

TB-pyridine cyano vinyl derivative with viscosity response and synthesis and application thereof
Technical Field
The invention belongs to the field of chemical synthesis, and in particular relates tobase-pyridine cyano vinyl derivatives, a synthesis method thereof and application thereof in viscosity response and endoplasmic reticulum targeting anti-tumor.
Background
Viscosity is one of the main parameters affecting various biological processes, which determines the mobility of the substance and the rate of diffusion-controlled reactions. In cells, viscosity has a great influence on the mass and signal transmission and interactions between biomacromolecules. Intracellular viscosity abnormalities are considered as important factors or indicators of many diseases and dysfunctions, including diabetes, infarction, hypertension, and the like, and therefore, monitoring the viscosity in cells in real time is of great importance for investigation and diagnosis of related diseases.
The traditional viscometer can not detect the intracellular viscosity, and the fluorescent small molecules have strong cell penetration capability and small damage to cells, so that the fluorescent small molecules can be used for monitoring the change of the intracellular viscosity and become a main selection target for designing and synthesizing novel intracellular viscosity response fluorescent probes.
The formation of dense polypeptide chains during misfolding and aggregation of proteins can lead to viscosity changes. The endoplasmic reticulum serves as an important organelle of cells, organically connects the nucleus, cytoplasm, and cell membrane into a whole in the cell, and is responsible for the transport of substances in the cell and is also a protein synthesis base. The viscosity probe with endoplasmic reticulum targeting capability can monitor viscosity change caused by protein aggregation in endoplasmic reticulum.
Pyridine has various physiological activities such as antibacterial, antitumor, antiinflammatory and antihypertensive properties. Meanwhile, pyridine has strong electrophilicity, can be used as an electron acceptor, and is widely applied to novel bipolar materials and organic devices. The cyano group has higher electron affinity, so that the cyano group can be used as a buffer layer for leading in and out electrons in an organic matter. Some cyano-substituted compounds (R-CN) can exhibit unique enhanced emission behavior in the solid state cyanovinyl groups can be combined with fluorescent groups to act as electron donors or electron acceptors in organic molecular synthesis. Thus, if cyanovinyl and pyridine are combined, both the electron withdrawing ability and AIE properties are enhanced.
Therefore, the invention designs and synthesizes the structure of D-pi-A by attracting electron fragments of cyanoethylene and pyridine on TB skeletonbase-pyridine cyanovinyl derivatives.
Disclosure of Invention
Technical problems: the invention aims to provide a TB-pyridine cyanovinyl derivative with viscosity response, and synthesis and application thereof, which are prepared by taking p-bromoaniline, paraformaldehyde, n-butyllithium, 4-pyridine acetylnitrile and the like as raw materials through multi-step reactionThe base-pyridine cyano vinyl derivative is applied to the fields of viscosity identification, endoplasmic reticulum positioning, anti-tumor and the like.
The technical scheme is as follows: the structural formula of the TB-pyridine cyano vinyl derivative with viscosity response is as follows:
the synthesis method of the TB-pyridine cyano vinyl derivative with viscosity response comprises the following steps:
step 1, 4-bromoaniline reacts with paraformaldehyde to obtain a first intermediate, wherein the reaction formula is as follows:
step 2, reacting the first intermediate with n-butyllithium to obtain a second intermediate, wherein the reaction formula is as follows:
step 3, the second intermediate and 4-pyridine acetyl nitrile are subjected to a coupling reaction to obtain a derivative, wherein the reaction formula is as follows:
the invention relates to an application of a TB-pyridine cyano vinyl derivative with viscosity response in preparing a viscosity probe.
The invention relates to application of a TB-pyridine cyano vinyl derivative with viscosity response in preparation of an endoplasmic reticulum targeting probe.
The application of the endoplasmic reticulum targeting probe is the positioning of the endoplasmic reticulum of human lung cancer A549 cells.
The invention relates to application of a TB-pyridine cyano vinyl derivative with viscosity response in preparation of anticancer drugs.
The application of the anti-cancer drugs in preparing the anti-cancer drugs aims at inhibiting the HpeG2 cells of human liver cancer and the A549 cells of human lung cancer.
The beneficial effects are that:
1. the synthesis method is simple and the post-treatment is convenient;
2. the product has excellent luminescence property: has large Stokes shift, excellent solid state luminescence and remarkable AIE properties.
3. The pH value application range is wide, and the pH value can be applied to human physiological environments;
4. a good response to viscosity is effective, and there is a possibility that a fluorescent probe is used as a viscosity response;
5. is easy to enter into living A549 cells, and has stronger targeting ability to endoplasmic reticulum (the Pearson coefficient Pr is 0.75).
6. The inhibition capability of HpeG2 cells under dark and light conditions (428 nm) is strong, which indicates that the HpeG2 cells have the potential of developing into anti-liver cancer drugs.
Drawings
FIG. 1 is a schematic illustration of the product derivative 6 of the example 1 HNMR spectrogram;
FIG. 2 is a schematic illustration of the product derivative 6 of the example 13 CNMR spectrogram;
FIG. 3a is the ultraviolet absorbance spectrum of derivative 6 in different solvents;
FIG. 3b is the fluorescence emission spectra of derivative 6 in different solvents;
FIG. 4 is a plot of (a) fluorescence emission spectra and (b) line for derivative 6 at different pH's;
FIG. 5 shows the THF/H ratio of derivative 6 at different ratios 2 O (v/v) a (a) fluorescence emission spectrum and a (b) line graph;
FIG. 6 shows the THF/H ratio of derivative 6 2 SEM image under O (v/v) (a) DMSO/H 2 O=1/9 (v/v) and (b) DMSO/H 2 O＝1/99(v/v)；
FIG. 7 is a plot of (a) fluorescence emission spectra and (b) line for derivative 6 at different viscosities;
FIG. 8 shows the fluorescence intensity of derivative 6 with different ions and molecules;
FIG. 9 is a plot of (a) fluorescence emission spectra versus (b) for compound 6 at different temperatures; a line graph of (c) fluorescence emission spectrum and (d) after combination with egg white;
FIG. 10 is co-localized fluorescence imaging of derivative 6 and ER-tracker Green co-processed HeLa cells;
FIG. 11 is a phototoxicity and dark toxicity test of derivative 6 on (a) A549 cells and (b) HpEG2 cells.
Detailed Description
The invention is further illustrated below with reference to examples.
Embodiments of the present invention are described in detail below. The examples described below are illustrative only and are not to be construed as limiting the invention. Those skilled in the art will appreciate that various changes and modifications can be made to the invention without departing from the spirit and scope thereof.
The following steps are as follows: 4-bromoaniline 1, paraformaldehyde 2, a first intermediate 3, a second intermediate 4, 4-pyridine acetyl nitrile 5 and a derivative 6.
The structural formula of the base-pyridine cyanovinyl derivative is shown in the following table:
TABLE 1 structural formula of derivative 6
The invention also provides the novelA process for the preparation of a base-pyridinecyanovinyl derivative comprising:
in the embodiment, the catalyst is prepared by taking p-bromoaniline, paraformaldehyde, n-butyllithium, 4-pyridine acetyl nitrile and the like as raw materials through coupling reaction. The method comprises the following steps:
the 4-bromoaniline 1 reacts with paraformaldehyde 2 to obtain a first intermediate 3, the first intermediate 3 reacts with n-butyllithium to obtain a second intermediate 4, and the second intermediate 4 reacts with 4-pyridine acetylnitrile 5 through coupling reaction to obtain a derivative 6.
By the above synthetic method, derivative 6 of the example was prepared:
4-Bromoaniline (50.0 mmol) and paraformaldehyde (100.0 mmol) were successively added to a 200.0mL round-bottomed flask, the flask was warmed to-15℃in a low-temperature tank, and trifluoroacetic acid (100.0 mL, after completion of dropwise addition for about 30 min) was slowly added dropwise to the flask under stirring, followed by reaction at room temperature for 7 days. After completion of the reaction (TLC trace), the mixture was poured into ice water, ph=9-10 was adjusted with aqueous ammonia, cooled to room temperature, extracted with dichloromethane (50.0 ml×3) and dried by spinning to give the crude product. Acetone is added, the mixture is heated until the crude product is completely dissolved, recrystallized at room temperature, filtered by suction, and washed by acetone, thus obtaining a first intermediate 3.
Synthesis of intermediate 3 of equation 1
(3) 3 (5.0 mmol) is added into a 100mL round bottom flask, after three times of air extraction, the flask is placed in a low-temperature tank to be heated to-78 ℃, 20.0mL of anhydrous tetrahydrofuran is added into the flask under stirring, 2.5mL of n-butyllithium is dropwise added, the mixture is reacted for 1h under the protection of argon, 0.6mL of LDMF is dropwise added, and the mixture is then placed at room temperature for 4h of reaction. After completion of the reaction by TLC, extraction with dichloromethane (30.0 mL. Times.3) was performed and the crude product was obtained by spin-drying. Purification of the crude product by column chromatography (V Petroleum ether :V Acetic acid ethyl ester Second intermediate 4 (33%) was obtained =5:1).
Equation 2 Synthesis of intermediate 4
(4) Sequentially adding a second intermediate 4 (1.0 mmol), 4-pyridine acetonitrile (1.2 mmol) and 30mL of anhydrous methanol into a 100mL round bottom flask, heating the reaction mixture to 80 ℃ under the protection of argon, tracking TLC until the reaction is complete, adding water for quenching, extracting (20.0 mL multiplied by 3) an organic phase with dichloromethane, and using anhydrous Na 2 SO 4 After drying, the crude product is obtained after spin drying. Purification of the crude product by column chromatography (V Petroleum ether :V Acetic acid ethyl ester =5:1) to give derivative 6 (77%).
Synthesis of (Z) -3- (8-bromo-6H, 12H-5, 11-methyldibenzo [ b, f ] [1,5] diazocine) -2- (pyridin-4-yl) acrylonitrile (6) of derivative 6 according to equation 3
1 HNMR(400MHz,DMSO-d 6 )δ8.84(d,J＝5.0Hz,2H),8.43(s,1H),8.04(d,J＝5.9Hz,2H),7.93(d,J＝8.5Hz,1H,Ar-H),7.68(s,1H,Ar-H),7.41-7.29(m,2H,Ar-H),7.25-7.11(m,2H),4.71(t,J＝15.8Hz,2H,-CH 2 -bridge),4.42-4.16(m,4H,TB-CH 2 *2). 13 CNMR(100MHz,DMSO-d 6 )δ152.8,148.8,147.3,146.5,131.2,130.5,130.3,130.0,129.4,129.1,128.4,127.5,125.9,121.6,117.4,105.0,66.2,58.4,58.3.
Optical Properties
The solvation effect of the compounds of the invention was tested, and the specific test protocol is as follows:
the derivative 6 is prepared by using Methanol (Methanol), dimethyl sulfoxide (DMSO), N-Dimethylformamide (DMF), tetrahydrofuran (THF), ethyl acetate (ethylacetate), and chloroform (CHCl) 3 ) Toluene (tolene), n-Hexane (n-Hexane) to give a concentration of 1×10 -5 mol·L -1 And testing the ultraviolet absorption spectrum and the fluorescence emission spectrum of the working fluid. As shown in fig. 3a-3 b.
As can be seen from fig. 3a-3b, as the polarity of the solution increases, the energy difference between pi-pi orbitals decreases and the uv absorption band undergoes a red shift, since the derivative 6 is more stable to pi orbitals than to pi orbitals; the fluorescence emission wavelength of the derivative 6 is red shifted, and the fluorescence intensity is lowered. This is because when the derivative 6 is in a strongly polar solution, the electrostatic interaction with the solvent increases, thereby stabilizing the excited state of the derivative 6, causing the fluorescence emission wavelength to red shift, indicating that the derivative 6 has an ICT effect.
The ultraviolet absorption and fluorescence emission spectra of derivative 6 in DMSO solution and its solid state fluorescence emission spectra were tested, with the following protocol:
weighing 10 -5 mol of 4-bromoaniline 1, second intermediate 4 and derivative 6, are fixed to a concentration of 1X 10 in DMSO solution -5 And (3) testing ultraviolet absorption, fluorescence emission and solid state fluorescence emission spectra of the fluorescent dye.
The spectral data of 4-bromoaniline 1, second intermediate 4 and derivative 6 are shown in table 2.
Table 24-spectral Data (DMSO) of bromoaniline 1, second intermediate 4 and derivative 6
a Ultraviolet absorption wavelength (slit is 2.5/5 nm) in the solution; b molar extinction coefficient epsilon=a/bC in 1×10 5 L·mol -1 ·cm -1 ； c Fluorescence emission wavelength in the solution; d stokes shift in solution; e relative fluorescence quantum yield (reference: quinine sulfate); f fluorescent brightness in L.mol -1 ·cm -1 ； g Solid state excitation wavelength (slit 5/5 nm); h solid state fluorescence emission wavelength; i solid Stokes displacement.
(1) The solution and solid λem of the derivative 6 are obviously red shifted, and the displacement of the solution and solid Stokes (155 nm and 102nm respectively) is obviously increased;
(2) The solution of derivative 6 has significantly increased relative fluorescence quantum yield.
This is probably due to the fact that after the 4-pyridine acetonitrile group is introduced into the derivative 6, the electron flow is promoted, the whole energy of the molecule is reduced, the fluorescence emission is easier, the maximum fluorescence emission wavelength is longer, and Stokes displacement is increased;
(3) C=c limits intramolecular rotation so that the molecule has a highly distorted structure, thereby enhancing solid state light emission intensity.
The above results demonstrate that combining the TB backbone with the 4-pyridinecyanoethylene fragment can amplify the advantages of both in light emitting properties, a new way to obtain products with excellent light emitting properties.
pH response
Preparation of derivative 6 to a concentration of 1X 10 in DMSO as solvent -4 mol·L -1 1.0mL of derivative 6 working solution is respectively measured in 9 volumetric flasks of 10.0mL, then 1.0mL of buffer solution with pH value of 2.2-10.0 (citric acid/disodium hydrogen phosphate system is selected when the pH value is 2.2-8.0, sodium bicarbonate/sodium carbonate system is selected when the pH value is 9.0-10.0) and DMSO are respectively added for volume fixation, so that the concentration of the buffer solution is 1 multiplied by 10 -5 molL -1 Its fluorescence emission spectrum (. Lambda.) was measured ex =365 nm, slit: 10/10nm, FIGS. 4a-4 b).
As can be seen from fig. 4a-4b, the fluorescence intensity of derivative 6 remained almost constant in the pH range of 2.2-10.0, indicating that derivative 6 has a broad pH application range.
AIE Property
Since derivative 6 is readily soluble in DMSO and poorly soluble in water, 6 is formulated at a concentration of 1X 10 -4 mol·L -1 Respectively weighing 1.0mL of working solution into 10 volumetric flasks of 10.0mL, then respectively adding 0.0-9.0mL of double distilled water into the 10 volumetric flasks of 10.0mL, and fixing the volume of DMSO to make the concentration of the double distilled water be 1X 10 -5 mol·L -1 (DMSO/H 2 O (v/v) is 1/9-9/1 in turn), and the derivative 6 is prepared to have the concentration of 1 multiplied by 10 -3 mol·L -1 100.0 mu L of working solution is measured in a 10.0mL volumetric flask, 9.9mL double distilled water is added into the 10.0mL volumetric flask, and DMSO is used for volume determination to ensure that the concentration is 1 multiplied by 10 -5 molL -1 So that DMSO/H 2 O=1/99 (v/v). The fluorescence emission spectra were measured as shown in FIGS. 5a-5b (lambda ex =365 nm, slit: 5/10 nm).
As can be seen from 5a-5b, when the water content is less than 90%, the fluorescence emitted by the system is weaker; when the water content reaches 99%, the fluorescence intensity is obviously enhanced. The possible reasons are: when the water content is 0-90%, the energy of the excited state of the derivative 6 is dissipated in a non-radiative transition mode, and the fluorescence signal is weak; when the volume fraction of poor solvent water reaches 99%, derivative 6 rapidly aggregates in the poor solvent system, so that the aromatic ring and conjugated double bond which could otherwise rotate freely become non-rotatable due to aggregation, thereby generating strong fluorescence emission. It follows that derivative 6 has typical AIE properties.
To explore the mechanism of formation of AIE properties of derivative 6, we observed derivative 6 in DMSO/H using a Scanning Electron Microscope (SEM) 2 O=1/9 (v/v) and DMSO/H 2 Topographical features at o=1/99 (v/v), as shown in fig. 6a-6 b.
As can be seen from fig. 6a-6 b: the derivative 6 is amorphous particles at a water content of 90% and the first intermediate 3 exhibits regular-shaped, uniform-sized rice-grain-like aggregates with an average diameter of 3 μm when the water content reaches 99%. It is shown that 6 can self-assemble into nano-aggregates at a water content of 99%, fluorescence is sharply enhanced, AIE characteristics are reflected, and the formation of stable nano-aggregates may be the reason for its AIE performance.
Viscosity response
Viscosity responsiveness to 6 was tested: preparation of derivative 6 to a concentration of 1×10 with methanol as solvent - 4 mol·L -1 Is a working fluid of (a). Taking 10 volumetric flasks of 10.0mL, adding 0.0-9.0mL glycerol respectively, taking 1.0mL working solution into the volumetric flasks, and metering methanol to volume to make its concentration 1×10 -5 mol·L -1 Fluorescence emission spectra (volume ratio of methanol/glycerol: 1/9 to 10/0 in this order) were measured as shown in 7a to 7b (λex=365 nm, slit: 5/10 nm).
From 7a to 7b, it is understood that the fluorescence intensity of the derivative 6 increases with an increase in viscosity. This is because the molecular rotor is free to rotate with lower viscosity, and the rotational motion consumes exciton energy and increases the non-radiative decay rate, resulting in weaker fluorescent signals of derivative 6; with the increase of viscosity, the free rotation of the molecular rotor is inhibited, and the non-radiative transition mode is weakened, so that the fluorescence of the molecular rotor is enhanced. The results demonstrate the potential of derivative 6 to become a viscosity responsive fluorescent probe.
Interference experiment
Checking common cation Fe 3+ 、Al 3+ 、Na + 、Ca 2+ 、Cu 2+ 、Cr 3+ And K + The method comprises the steps of carrying out a first treatment on the surface of the Anionic CO 3 2- 、HCO 3 - 、CH 3 COO - 、PO 4 2- 、SO 4 2- 、SCN - And HS (high speed) - The method comprises the steps of carrying out a first treatment on the surface of the Effects of biological thiols Cys, hcy and GSH and 90% glycerol (left to right 2-18,1 as blank) on the fluorescence emission spectrum of derivative 6 as shown in FIG. 8 (lambda) ex =365 nm, slit: 10/10 nm).
The result shows that after various anions and cations and biological thiols are added, the fluorescence intensity of the derivative 6 is basically unchanged, and the fluorescence intensity of the derivative 6 in 90% glycerol is obviously enhanced, which indicates that the derivative 6 can realize specific detection of viscosity in a complex biological environment.
Protein aggregation assay
The formation of dense polypeptide chains during misfolding and aggregation of proteins can lead to viscosity changes [74] . The physicochemical properties of the protein are changed after the protein is denatured, and hydrophobic groups in the molecule are exposed, so that the condensation speed of the protein is increased, the protein is separated out from the aqueous solution, and the viscosity of the protein is increased. Therefore, the viscosity change in the protein aggregation process is simulated by adopting the egg white thermal denaturation process, and the viscosity change in the denaturation process is monitored by using the derivative 6 to observe the fluorescence change.
The fluorescence change of the derivative 6 at 0-100deg.C was first tested (FIGS. 9a-9 b), and the results showed that the fluorescence intensity of the derivative 6 at 0-100deg.C was not significantly changed, indicating that it has good thermal stability (lambda) ex =365 nm, slit: 10/10 nm).
The derivative 6 is mixed with a proper amount of egg white, the protein gradually gathers and the viscosity increases along with the temperature rise, and the fluorescence of the derivative 6 gradually increases, so that the derivative can be used for monitoring the viscosity change when the protein gathers, and has the potential of becoming a viscosity response probe for the protein gathers (figures 9c-9 d).
ER localization experiments
ER is an important cellular organelle of cells, organically connects the nucleus, cytoplasm and cell membrane into a whole in the cells, and is responsible for the transport of substances in the cells and is also a synthesis base of proteins and lipids. While cyano group is well liposoluble and can be localized in theory to ER. Therefore, reasonable co-localization experiments were designed for verification.
After first incubating ER commercial probes ER-tracker Green and derivative 6 with HeLa cells under appropriate conditions for 30min, respectively, washing twice with Phosphate Buffered Saline (PBS), adding PBS for confocal imaging, the results are shown in FIG. 10.
The results show that derivative 6 can easily penetrate living HeLa cells and co-localize with ER-tracker green, pr=0.75, indicating that it can easily enter HeLa cells and localize precisely to ER.
In vitro photodynamic therapy
Taking human non-small cell lung cancer (A549) cells and human liver cancer (HepG 2) cells as models, and detecting cytotoxicity of the derivative 6 on the A549 cells and the HepG2 cells by adopting an MTT method. A549 cells and HepG2 cells were seeded in 96-well plates (1×10) -5 mu.L of medium was added to each well, CO at 37 ℃ 2 After incubation for 24h in the incubator, compound 6 was added at different concentrations to the inoculated cells for incubation for 24h. The microwell plates were then rinsed 3 times with PBS buffer and 10. Mu.L of MTT solution was added to each well for an additional 4h of incubation. Removing culture medium in the wells, adding 150 μl of DMSO into each well to dissolve blue-violet formazan (formazan) crystals in the cells, placing on a shaking table, and shaking at low speed for 5-7min to dissolve the crystalline substance sufficiently. And finally, measuring absorbance values of each hole at 560nm and 670nm by adopting an enzyme-linked immunosorbent assay. Cytotoxicity was calculated by the following formula:
％viability＝[∑(A i /A 0 ×100)/n]
in which A i Absorbance values for different concentrations of the compound, respectively; a is that 0 Average absorbance values for control wells without added compound; n (=3) represents three parallel experiments.
The MTT assay was used to detect dark and phototoxicity of derivative 6 to HpeG2 cells and to A549) cells. The light source was 365nm, the control group was not subjected to light treatment, and absorbance values at 560nm and 670nm of each well were measured using an enzyme-linked immunosorbent assay. Dark toxicity and phototoxicity of derivative 6 on A549 and HpeG2 cells are shown in FIGS. 11a-11 b.
TABLE 5 half-maximal inhibition of derivatives 6 (IC) 50 )
Half inhibition of HpeG2 and A549 cells by derivative 6 is shown in Table 5, and the results indicate that IC for HpeG2 and A549 cells 50 76.5 and 11.2. Mu. Mol.L, respectively -1 While under the illumination condition (428 nm), the inhibition rates of HpeG2 cells and A549 cells are 36.2 and 5.5 mu mol.L respectively -1 It is shown to have excellent PDT effect. And the inhibition capability of HpeG2 cells under dark and light conditions (428 nm) is strong, which shows that the composition has the potential of developing into anti-liver cancer drugs.
The foregoing is only a preferred embodiment of the invention, it being noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the present invention, and such modifications and adaptations are intended to be comprehended within the scope of the invention.

Claims (7)

1. A TB-pyridinecyanovinyl derivative having a viscosity response, characterized by the structural formula:
2. a method of synthesizing a viscosity responsive TB-pyridinecyanovinyl derivative according to claim 1, comprising the steps of:
step 1, 4-bromoaniline (1) reacts with paraformaldehyde (2) to obtain a first intermediate (3), and the reaction formula is as follows:
step 2, the first intermediate (3) reacts with n-butyllithium to obtain a second intermediate (4), and the reaction formula is as follows:
step 3, the second intermediate (4) and 4-pyridine acetyl nitrile (5) are subjected to a coupling reaction to obtain a derivative (6), wherein the reaction formula is as follows:
3. use of a TB-pyridinecyanovinyl derivative having a viscosity response according to claim 1 in the preparation of a viscosity probe.
4. Use of a TB-pyridinecyanovinyl derivative having a viscosity response according to claim 1 in the preparation of an endoplasmic reticulum targeting probe.
5. The use of claim 4, wherein the use of the endoplasmic reticulum targeting probe is for the localization of the endoplasmic reticulum of human lung cancer a549 cells.
6. Use of a TB-pyridinecyanovinyl derivative having a viscosity response according to claim 1 in the preparation of an anticancer drug.
7. The use according to claim 6, wherein the use in the preparation of an anticancer drug is directed against inhibition of human liver cancer HpeG2 cells and human lung cancer a549 cells.
CN202310984557.2A 2023-08-07 2023-08-07 TB-pyridine cyano vinyl derivative with viscosity response and synthesis and application thereof Pending CN117003759A (en)

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