CN111675921A - CYPY and application thereof in preparation of antitumor drugs - Google Patents
CYPY and application thereof in preparation of antitumor drugs Download PDFInfo
- Publication number
- CN111675921A CN111675921A CN202010516755.2A CN202010516755A CN111675921A CN 111675921 A CN111675921 A CN 111675921A CN 202010516755 A CN202010516755 A CN 202010516755A CN 111675921 A CN111675921 A CN 111675921A
- Authority
- CN
- China
- Prior art keywords
- cypy
- tumor
- colorectal cancer
- dld
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/10—The polymethine chain containing an even number of >CH- groups
- C09B23/107—The polymethine chain containing an even number of >CH- groups four >CH- groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- 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
Abstract
The invention belongs to the technical field of chemical medicines, and relates to application of 1, 5-bis [ N- (3, 5-bis (2- (2-methoxyethoxy) ethoxy) benzyl-2, 3, 3-trimethyl-3H-indole ] -3- (4-pyridine) pentacycyanine bromide dye (CYPY for short) in preparation of antitumor drugs. MTT results show that: CYPY can obviously inhibit the activity of colorectal cancer cells in DLD-1 and SW480 cells. The results of animal experiments show that: CYPY can obviously inhibit the growth of subcutaneous tumor-bearing tumors of a human colorectal cancer cell line DLD-1BALB/C nude mouse and can be used for preparing antitumor drugs. The compound CYPY is developed as a novel anti-tumor medicament or an auxiliary component thereof, has obvious tumor inhibition effect, and provides a new treatment way and means for treating and curing tumors.
Description
Technical Field
The invention belongs to the technical field of chemical medicines, and particularly relates to application of a novel pentamethine cyanine dye CYPY in preparation of antitumor drugs.
Background
Along with the increase of global population, environmental problems caused by aging, environmental pollution and other factors are more and more prominent, and the detection rate and the incidence rate of malignant tumors are on the trend of rising year by year; tumors have become one of the most serious diseases threatening mankind in modern society, and related investigations have shown that cancer is the leading cause of death in developing countries and the second cause of death in developed countries. Cancer is called "senile disease", but in recent years, the trend of cancer to be younger is also becoming more and more apparent. With the application of new diagnosis and treatment technologies and the continuous development of chemotherapeutic drugs, the prognosis of tumor patients is greatly improved, but the overall survival rate of the patients is not remarkably improved. At present, among the numerous approaches for tumor treatment, surgery and chemotherapy are mainly used. Surgical treatment is associated with a greater degree of trauma to the patient's body, and the stage of progression of the tumor determines the feasibility of the surgery. Current chemotherapeutic drugs also have varying degrees of side effects. The development of novel antitumor drugs is still the first task of many relevant researchers.
The cyanine dye has the advantages of easy synthesis, good fluorescence effect, adjustable emission spectrum range, convenience for combination with biomolecules and the like, and is widely applied to living biological cell marking. The cyanine dye can be used for gene detection, protein detection, fluorescent probes and the like in the medical field. However, with the development of biotechnology, synthesized cyanine dyes cannot meet the application requirements. Therefore, research and development of novel cyanine dyes are of great significance to the biomedical field. The design and synthesis of a novel pentamethine cyanine dye CYPY and the application thereof in the preparation of antitumor drugs are the first research of the subject group, and experiments show that the compound has the potential of treating colorectal cancer, and no research on the related antitumor activity of the compound exists at present.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a novel material CYPY and a novel application thereof as a medicine, namely an application of CYPY in preparing an anti-colorectal cancer medicine.
In order to achieve the purpose, the invention adopts the following technical scheme:
the application of CYPY in preparing antitumor drugs is shown in the following chemical structure:
the relevant properties are as follows:
chemical name: 1, 5-bis [ N- (3, 5-bis (2- (2-methoxyethoxy) ethoxy) benzyl-2, 3, 3-trimethyl-3H-indole ] -3- (4-pyridine) pentacyanine bromide dye (referred to as CYPY for short).
The molecular formula is as follows: c72H98N3O16(ii) a Molecular weight: 1261.56, respectively; the detection mode is as follows:1H NMR、13c NMR and ESI-MS; the characteristics are as follows: the product is blue solid granule; the source is as follows: synthesized in the laboratory. Pharmacological properties: is soluble in water。
Specifically, the CYPY is applied to preparation of an anti-colorectal cancer medicament, and the compound is mainly used for resisting colorectal cancer DLD-1 cells, colorectal cancer SW480 cells and the like.
Further, the concentration of the anti-tumor effect of the CYPY is 0.2 to 25 mu M.
The invention provides a method for inhibiting the proliferation activity of in vitro tumor cells, which is to add CYPY into a tumor cell culture solution, wherein the concentration of the added CYPY is 0.2 to 25 mu M. The tumor cells are a colorectal cancer cell line DLD-1 and a colorectal cancer cell line SW 480.
The invention provides a method for inhibiting tumor growth in vivo, comprising the step of injecting CYPY into a BALB/C nude mouse through a paraneoplastic tissue, wherein the injection dosage of the CYPY is 1 mg/mL. The nude mouse in vivo model can be a colorectal cancer cell line DLD-1BALB/C nude mouse subcutaneous tumor-bearing model.
The invention also provides an anti-tumor medicament, and the active component of the anti-tumor medicament is CYPY.
The CYPY provided by the invention plays an anti-tumor role through photothermal activity and photodynamic pathways. Namely, the antitumor drug containing the active ingredient CYPY can obviously inhibit the cell activity of DLD-1 and SW480 cells of colorectal cancer tumors through photothermal effect and photodynamic.
Compared with the prior art, the invention has the beneficial effects.
The invention provides an application of CYPY in preparing an anti-tumor medicament. MTT results show that: CYPY dose-dependently inhibited the proliferation of colorectal cancer cell lines DLD-1 and SW 480. The results of animal experiments show that: CYPY remarkably inhibits the growth of subcutaneous tumor-bearing tumors of a human colorectal cancer cell line DLD-1BALB/C nude mouse. The small molecular compound CYPY is developed as a new anti-tumor medicament or an auxiliary component, has obvious tumor inhibition effect, and provides a new treatment way and means for treating and curing tumors.
Drawings
FIG. 1.CYPY Structure identification1H NMR(a)、13C NMR (b) and ESI-MS (C) data.
FIG. 2 CYPY inhibits colorectal cancer DLD-1 and SW480 cell viability by light effect.
FIG. 3 CYPY inhibits colorectal DLD-1 and SW480 cell viability by photothermal and photodynamic action
FIG. 4 CYPY significantly inhibited the growth of subcutaneous tumor-bearing colorectal cancer DLD-1BALB/C nude mice.
Detailed Description
In order to make the technical purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention is further described with reference to specific examples, but the implementation is intended to explain the present invention and should not be construed as a limitation of the present invention, and those who do not specify specific techniques or conditions in the examples follow the techniques or conditions described in the literature in the field or follow the product specification.
Application example 1, CYPY Synthesis and Structure identification.
CYPY was synthesized according to the following scheme.
To a 50mL two-necked round bottom flask was added 2-phenylpropanedialdehyde (18.7mg, 0.13mmol, 1.0eq), compound 3(144.0mg, 0.25mmol, 2.0eq), oxygen removed for 30min, oxygen removed glacial acetic acid 3mL and acetic anhydride 3mL were added, stirred for 10min, and reacted at 110 ℃ for 3h under argon. TLC monitoring reaction is finished, cooling to room temperature, and rotary evaporation is carried out to remove the solvent to obtain a crude product. And (3) separating the crude product by column chromatography (200-mesh silica gel 300 meshes, mobile phase: methanol: dichloromethane: 1:20) to obtain a blue solid compound CYPY: 89.5mg, yield: 56.6 percent.
1H NMR(400MHZ,DMSO-d6)8.57(d,J＝4.8Hz,2H),8.42(d,J＝14.4Hz, 2H),7.71(d,J＝7.2Hz,2H),7.51(d,J＝8.0Hz,2H),7.42(t,J＝7.6Hz,2H),7.32 (t,J＝7.6Hz,2H),6.85(d,J＝4.8Hz,2H),6.48(s,2H),6.08(s,4H),5.61(d,J＝ 14.4Hz,2H),5.02(s,4H),3.99(m,8H),3.71(m,8H),3.56-3.47(m,24H),3.40-3.37 (m,8H),3.20(s,12H),1.77(s,12H)；13C NMR(100MHZ,DMSO-d6)173.71, 160.03,152.36,150.37,142.68,142.32,141.04,137.04,128.66,125.37,124.53, 122.71,111.42,105.01,101.76,99.89,71.24,69.90,69.76,69.57,68.80,67.20, 58.00,49.19,46.83,27.01；MS(ESI):calcd for[M]+1261.56, found 1261.10. CYPY structure identification1H NMR (A) is shown in FIG. 1-A, HRMS (B) data is shown in FIG. 1-B, ESI-MS data is shown in FIG. 1-C.
Application example 2, CYPY significantly inhibited the colorectal cancer cell lines DLD-1 and SW480 cell viability.
DLD-1 and SW480 cells were as per 3 × 10, respectively3Inoculating to 96-well plate with 5% CO2100U/mL penicillin and 100. mu.g/mL streptomycin in RPMI 1640 complete medium at 37 ℃ until the cells are completely attached to the wall, adding different concentrations (25. mu.M, 12.5. mu.M, 6.25. mu.M, 3.125. mu.M, 1.56. mu.M, 0.78. mu.M, 0.39. mu.M, 0.2. mu.M) of CYPY, setting 5 duplicate wells for each concentration, abandoning the culture solution after 48h of drug action, and determining the cell viability by the MTT method.
The determination method comprises the following steps: adding a pre-prepared MTT reaction solution into 15 mu L/hole, continuously culturing for 4h, sucking and removing the supernatant, adding DMSO into 100 mu L/hole to dissolve the reduction product, reacting for 5min in a dark place, reading the absorbance value at 490nm, calculating the cell survival rate, and determining the absorbance value of the CYPY intervention hole/the control hole as the cell survival rate.
IC50The concentration of the inhibitor at which the cell growth was inhibited by half, i.e., the concentration of CYPY at which the number of DLD-1 and SW480 cells of the colorectal cancer cell lines was half of that of the control group, respectively.
As a result: IC of CYPY on colorectal cancer DLD-1 cells50The value was 7.58. mu.M, see FIG. 2-A; IC for colorectal cancer SW480 cells50The value was 6.41. mu.M, as shown in FIG. 2-B.
DLD-1 and SW480 cells were as described in 3 × 103Perwell inoculation into 96 well plates with 5% CO2100U/mL penicillin and 100 mug/mL streptomycin in RPMI 1640 complete culture medium at 37 ℃ until cells are completely attached to the wall, adding CYPY with different concentrations (25 muM, 12.5 muM, 6.25 muM, 3.125 muM, 1.56 muM, 0.78 muM, 0.39 muM and 0.2 muM respectively), setting 3 multiple wells for each concentration, giving 0.5W near infrared light after the drug acts for 24h, irradiating each well for 2min, continuing to culture for 24h, abandoning the culture solution, and determining the cell viability by MTT reagent.
As a result: CYPY adding medicineAfter 24h and 0.5W illumination, the lethality of the cell for the colorectal cancer is obviously enhanced, and the IC of the cell for the DLD-1 cell for the colorectal cancer50The value was 2.27. mu.M, see FIG. 2-C; IC for colorectal cancer SW480 cells50The value was 0.75. mu.M, as shown in FIG. 2-D.
Application example 3, CYPY inhibited the colorectal cancer cell lines DLD-1 and SW480 cell viability by photothermal and photodynamic effects.
DLD-1 and SW480 cells were as described in 3 × 103Perwell inoculation into 96 well plates, 5% CO2100U/mL penicillin and 100 mu g/mL streptomycin in RPMI 1640 complete culture medium at 37 ℃ until cells are completely attached to the wall, adding CYPY with different concentrations (25 mu M, 12.5 mu M, 6.25 mu M, 3.125 mu M, 1.56 mu M, 0.78 mu M, 0.39 mu M and 0.2 mu M respectively) and simultaneously adding 5mM N-acetyl-L-cysteine (NAC), wherein the NAC is an antioxidant, effectively inhibits the damage effect of photodynamic activity to the cells by active oxygen, 3 multiple wells are set for each concentration, the medicine is acted for 24h, 0.5W near infrared illumination is given, each well is irradiated for 2min, the culture is continued for 24h, the culture solution is discarded, and the cell activity is measured by MTT reagent to determine the photodynamic performance of the CYPY.
DLD-1 and SW480 cells were as described in 3 × 103Perwell inoculation into 96 well plates, 5% CO2100U/mL penicillin and 100 mu g/mL streptomycin in RPMI 1640 complete culture medium at 37 ℃ until cells are completely attached to the wall, adding CYPY with different concentrations (25 mu M, 12.5 mu M, 6.25 mu M, 3.125 mu M, 1.56 mu M, 0.78 mu M, 0.39 mu M and 0.2 mu M respectively), setting 3 multiple wells for each concentration, acting the drugs for 24h, placing a 96-well plate on ice, giving 0.5W near infrared light, irradiating each well for 2min, continuing culturing for 24h, abandoning the culture solution, and measuring the cell activity by using an MTT reagent to preliminarily determine the photothermal performance of the CYPY.
Accurately weighing a certain amount of sample with analytical balance to obtain 1 × 10-3And (3) taking the aqueous solution of M as mother liquor, and storing the mother liquor in a refrigerator for later use. During the test, the mother liquor is taken out and naturally raised to the room temperature, 500 mu L of the mother liquor is taken in a 5mL volumetric flask by a pipette, water is added to the volumetric flask to reach the scale, and the volumetric flask is shaken up to obtain 100 mu M stock solution. The stock solution is diluted in a gradient way to be prepared into aqueous solutions to be detected with different concentrations. Taking 2mL of blank aqueous solution and aqueous solution to be detected in a 24-well plate, andrespectively using (660nm, 0.5 w/cm)2) The laser single hole was continuously irradiated for 2min while temperature changes were recorded with a near infrared imager at 0, 0.5, 1, 1.5 and 2min, respectively.
The result shows that CYPY can obviously inhibit the activity of DLD-1 and SW480 cells of colorectal cancer through photothermal effect and photodynamic, as shown in figure 3, wherein figures 3-A and 3-B are respectively used for measuring the activity photodynamic performance of the CYPY for inhibiting the DLD-1 and SW480 cells of the colorectal cancer cell lines; FIGS. 3-C and 3-D are the measurement of CYPY inhibiting the photo-thermal properties of DLD-1 and SW480 cell viability, respectively, of colorectal cancer cell lines; FIG. 3-E is a graph showing the temperature change of CYPY at various concentrations as a function of the irradiation duration during the irradiation with 660nm near-infrared laser light.
Application example 4.CYPY inhibits growth of subcutaneous tumor-bearing colorectal cancer DLD-1 cells BALB/C nude mice.
The determination method comprises the following steps: establishing a tumor-bearing model of a colorectal cancer DLD-1BALB/C nude mouse in a subcutaneous injection mode, performing CYPY intervention on a tail vein according to a dose of 1mg/mL, detecting the accumulation level of CYPY in tumor tissues by using a small animal living body imaging system at different time points 0-72h after intervention, determining the tissue targeting property of the CYPY and determining the 660nm near infrared light irradiation time. Establishing a tumor-bearing model under a colorectal cancer DLD-1BALB/C nude mouse in a subcutaneous injection mode, giving CYPY intervention treatment to a tail vein according to a dose of 1mg/mL, giving 0.5W near infrared light for 2min according to the time determined by living body imaging of a small animal, performing euthanasia on the nude mouse, and cutting a tumor tissue and a main organ; determining the effect of CYPY on inhibiting the growth of subcutaneous tumor-bearing of colorectal cancer DLD-1BALB/C nude mice.
As a result: CYPY significantly accumulated to subcutaneous tumor-bearing tissue in nude mice with colorectal cancer DLD-1BALB/C within 0-48 hours after dry administration of CYPY in the tail vein and peaked the fourth hour after injection. CYPY significantly inhibits the growth of subcutaneous tumor-bearing tumor of a colorectal cancer cell line DLD-1BALB/C nude mouse, and the CYPY has no significant influence on the heart, the liver, the spleen, the lung and the kidney of the nude mouse, as shown in figure 4, wherein A is an imaging graph of the nude mouse living body, B is a graph of tumor volume changing with treatment time, C is a statistical graph of tumor-bearing weight, D is an overall image of dissected tumor, E is a graph of heart index, F is a graph of liver index, G is a graph of spleen index, H is a graph of lung index, I is a graph of kidney index, and J is a graph of weight changing with treatment time of the nude mouse.
From the above experimental results it can be seen that: CYPY can remarkably inhibit the activity of DLD-1 and SW480 cells of colorectal cancer tumors through photothermal effect and photodynamic effect, remarkably inhibit the growth of subcutaneous tumor-bearing of a colorectal cancer cell line DLD-1BALB/C nude mouse, and can be used for preparing antitumor drugs. The small molecular compound CYPY is developed as a new anti-tumor medicament or an auxiliary component thereof, has obvious tumor inhibition effect, and provides a new treatment way and means for treating and curing tumors.
Claims (7)
1. The compound 1, 5-bis [ N- (3, 5-bis (2- (2-methoxyethoxy) ethoxy) benzyl-2, 3, 3-trimethyl-3H-indole ] -3- (4-pyridine) pentacyanine bromide salt dye is characterized in that the dye is abbreviated as CYPY; the chemical structure of CYPY is shown below:
2. the application of 1, 5-bis [ N- (3, 5-bis (2- (2-methoxyethoxy) ethoxy) benzyl-2, 3, 3-trimethyl-3H-indole ] -3- (4-pyridine) pentacryanine bromide salt dye in preparing antitumor drugs.
3. The use of a CYPY according to claim 2 for the preparation of an anti-tumor medicament, wherein the CYPY inhibits the viability of DLD-1 or SW480 cells of a colorectal cancer cell line.
4. The use of a CYPY according to claim 3 in the preparation of an anti-tumor medicament, wherein the CYPY inhibits colorectal cancer cells at a concentration of from 0.2 μ M to 25 μ M.
5. The use of CYPY in the preparation of an anti-tumor medicament according to claim 3, wherein the CYPY inhibits the growth of subcutaneous tumor-bearing cancer in colorectal cancer cell line DLD-1BALB/C nude mice at a dose of 1 mg/mL.
6. The use of CYPY according to claim 2 for the preparation of an anti-tumor medicament, wherein CYPY exerts an anti-tumor effect by photothermal activity or photodynamic.
7. The use of CYPY according to claim 2 for the preparation of an anti-tumor medicament, wherein CYPY exerts an anti-tumor effect via the iron death, necrosis or apoptosis pathway.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010516755.2A CN111675921B (en) | 2020-06-09 | 2020-06-09 | CYPY and application thereof in preparation of antitumor drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010516755.2A CN111675921B (en) | 2020-06-09 | 2020-06-09 | CYPY and application thereof in preparation of antitumor drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111675921A true CN111675921A (en) | 2020-09-18 |
| CN111675921B CN111675921B (en) | 2021-12-14 |
Family
ID=72435627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010516755.2A Active CN111675921B (en) | 2020-06-09 | 2020-06-09 | CYPY and application thereof in preparation of antitumor drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111675921B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113736281A (en) * | 2021-09-07 | 2021-12-03 | 河南大学 | Cy7-Cl and application thereof in preparation of anti-colorectal cancer drugs |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103073909A (en) * | 2013-01-30 | 2013-05-01 | 河南大学 | Water-soluble asymmetric indocyanine fluorescent dye and preparation method thereof |
| WO2018206126A1 (en) * | 2017-05-08 | 2018-11-15 | Vysoká škola chemicko-technologická v Praze | Imaging agents and methods |
-
2020
- 2020-06-09 CN CN202010516755.2A patent/CN111675921B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103073909A (en) * | 2013-01-30 | 2013-05-01 | 河南大学 | Water-soluble asymmetric indocyanine fluorescent dye and preparation method thereof |
| WO2018206126A1 (en) * | 2017-05-08 | 2018-11-15 | Vysoká škola chemicko-technologická v Praze | Imaging agents and methods |
Non-Patent Citations (1)
| Title |
|---|
| TOMÁŠ BRÍZA等: "Pentamethinium salts as ligands for cancer: Sulfated polysaccharide co-receptors as possible therapeutic target", 《BIOORGANIC CHEMISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113736281A (en) * | 2021-09-07 | 2021-12-03 | 河南大学 | Cy7-Cl and application thereof in preparation of anti-colorectal cancer drugs |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111675921B (en) | 2021-12-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107056772A (en) | Bifunctional molecule and its preparation and the application of BET degradeds are induced based on cereblon parts | |
| CN109776380A (en) | It is applied in the bis- targeting near infrared fluorescent probe preparations of IR780 and tumour diagnosis and treatment | |
| CN106866743A (en) | Tumor-targeting metal complex and synthetic method and application | |
| CN104829596B (en) | Pyrrole-substituted indolinone derivative and preparation method thereof, composition including derivative, and application of derivative | |
| CN111592482B (en) | PH reversible activation type photo-thermal/photodynamic/fluorescent integrated probe molecule | |
| CN111377975B (en) | Novel mitochondrion-targeted iridium complex and preparation method and application thereof | |
| CN111675921B (en) | CYPY and application thereof in preparation of antitumor drugs | |
| CN105732681A (en) | Fluorescent diagnosis and treatment reagent development for diagnosing and treating non-small cell lung cancer (NSCLC) and application of cells thereof | |
| CN113292541A (en) | Nitroreductase responsive diagnosis and treatment integrated probe and preparation method and application thereof | |
| CN111205276A (en) | Micro-nano structure formed by self-assembly of organic small molecular compounds and application thereof | |
| CN111574499B (en) | Cy5-650 and application thereof in preparation of antitumor drugs | |
| CN111675920B (en) | PCPS and application thereof in preparation of antitumor drugs | |
| CN111494628B (en) | Application of pentamethine cyanine dye Cy5-671 in preparation of antitumor drugs | |
| US20230158176A1 (en) | Near-infrared fluorescent small-molecule probe, synthesis method and application thereof | |
| CN111675919B (en) | PCP and application thereof in preparing antitumor drugs | |
| CN111196922B (en) | Application of pH-sensitive beta-carboline derivative fluorescent probe in tumor fluorescence imaging | |
| CN115011139A (en) | Non-heavy atom photosensitizer based on cyanine dye structure and synthesis method and application thereof | |
| Wang et al. | Design, synthesis and application of near-infrared fluorescence probe IR-780-Crizotinib in detection of ALK positive tumors | |
| CN106860449A (en) | Purposes of the matrine derivative in diabetes are treated | |
| CN111569069A (en) | Tumor double-targeting diagnosis and treatment photosensitizer and preparation method and application thereof | |
| CN111925369A (en) | Beta-carboline cyano furan derivatives, preparation method and application thereof | |
| CN111635350B (en) | PCPC and application thereof in preparation of antitumor drugs | |
| CN109503495B (en) | 2-imine benzimidazole compound and medical application thereof | |
| CN115368368A (en) | 8-indole [4,3-c ] pyrimido [1,2,4] triazole derivative, and preparation method and application thereof | |
| CN115433219B (en) | Polar fluorescent probe with photodynamic property and preparation method and application thereof |
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 |