Fluorophore-loaded selenium-containing small molecule as well as preparation method and application thereof

Abstract

According to the fluorophore-loaded selenium-containing small molecule and the preparation method and application thereof, the small molecule has a good killing effect on tumor cells, can specifically target mitochondria and serves as a mitochondria developing agent. The small molecule can be used for diagnosis and treatment integration of tumor treatment.

Description

Technical Field

[0001] The invention belongs to the technical field of synthetic drug chemistry, and particularly relates to a selenium-containing small molecule loaded with a fluorescent group, and also relates to a preparation method of the selenium-containing small molecule loaded with a fluorescent group, and application of the selenium-containing small molecule in anti-tumor drugs. Background Art

[0003] Selenium is an essential trace element for the human body. Selenium can participate in various physiological processes through at least 25 eukaryotic selenoproteins. Among them, organic selenium compounds have been developed and studied the most. Compared with inorganic selenium compounds, organic selenium compounds have lower toxicity and higher biological activity. Various organic selenium compounds have been reported. Selenium-containing heterocyclic compounds are a large class of selenium compounds with various biological properties such as anti-cancer, anti-inflammatory and antiviral. Among them, selenadiazoles are very valuable agents in medicinal chemistry. Indole-derived hemicyanine dyes are well-known for their wide application in many research fields. Due to their unique π-conjugated structure, they exhibit rich colors and fluorescence properties in light absorption and emission. These properties also make them more and more widely used in biomarkers.

[0004] Therefore, by combining fluorescent groups with selenadiazole functional molecules with anti-tumor activity, the dual purposes of labeling and killing tumors can be achieved, which has great research significance for realizing the integrated diagnosis and treatment of tumors. Summary of the invention

[0005] In view of the above-mentioned shortcomings of the prior art, the purpose of the present invention is to connect a fluorescent group with a biomarker function and a selenadiazole pharmacological group with a tumor-killing effect through an ester bond, so as to achieve integrated diagnosis and treatment of tumors.

[0006] The present application provides a selenium-containing small molecule loaded with a fluorescent group, which is prepared by the following reaction formula:

[0007]

[0008] The preparation method of a selenium-containing small molecule loaded with a fluorescent group comprises the following steps:

[0009] (1) Synthesis of PhSe;

[0010] (2) Synthesis of miCy-OH;

[0011] (3) Synthesis of miCy-Se: A mixture of compounds PhSe, miCy-OH, 4-dimethylaminopyridine and 1-ethyl-(3-dimethylaminopropyl)carbodiimide was dissolved in anhydrous CH2Cl2 and stirred at room temperature overnight. The reaction was completed by TLC, and the mixture was concentrated under reduced pressure. The solid residue was purified by silica gel chromatography to obtain the target compound miCy-Se.

[0012] Specifically, in step (3), a mixture of 0.8-1.2 parts of compound PhSe, 0.4-0.6 parts of miCy-OH, 0.8-1.2 parts of 4-dimethylaminopyridine and 0.8-1.2 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide is dissolved in anhydrous CH2Cl2 and stirred overnight at room temperature; the above-mentioned amounts are measured by the amount of substance. The preparation method according to claim 1 is characterized in that the step (1) specifically comprises: mixing 3,4-diaminobenzoic acid and selenium dioxide in an aqueous solution, adding concentrated hydrochloric acid dropwise and stirring at room temperature, filtering the product, washing with water, washing with ethanol, and vacuum drying to obtain compound PhSe.

[0013] Specifically, in step (1), the molar ratio of 3,4-diaminobenzoic acid to selenium dioxide is 1:1 to 1-1.2.

[0014] Specifically, the step (2) specifically includes: first, adding 1,1,2-trimethyl-1H-benzo[e]indole and iodoethane to a round-bottom flask containing acetonitrile under nitrogen protection; stirring and refluxing the mixed solution at a certain temperature; removing the solvent by a rotary evaporator, and washing the crude product with petroleum ether for multiple times to obtain the compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium; dissolving the compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium and 6-hydroxy-2-naphthaldehyde in EtOH, and then dropping a small amount of piperidine; heating the mixture to reflux overnight; after cooling the mixture to room temperature, removing the solvent by a rotary evaporator, and removing the solvent from the crude product by a rotary evaporator; purifying the crude product by silica gel flash chromatography using dichloromethane / methanol as an eluent to obtain a yellow solid miCy-OH.

[0015] Specifically, the following steps are included:

[0016] (1) Synthesis of PhSe: 3,4-diaminobenzoic acid (1.54 g, 10 mmol) and selenium dioxide (1.11 g, 10 mmol) were mixed in an aqueous solution, concentrated hydrochloric acid was added dropwise and stirred at room temperature for 2 h; the product was filtered, washed with water and ethanol, and dried in vacuum to obtain compound PhSe;

[0017] (2) Synthesis of miCy-OH: First, 1,1,2-trimethyl-1H-benzo[e]indole (500 mg, 2.39 mmol) and iodoethane (745 mg, 4.78 mmol) were added to a round-bottom flask containing 10 mL of acetonitrile under nitrogen protection; the mixed solution was stirred and refluxed at 75°C, and the reaction was monitored by TLC; the solvent was removed by rotary evaporation, and the crude product was washed with petroleum ether several times to obtain compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium without purification; compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium (249 mg, 1.05 mmol) and 6-hydroxy-2-naphthaldehyde (172.2 mg, 1 mmol) were dissolved in 20 mL of 4% paraffin wax; EtOH, and then a small amount of piperidine was added dropwise; the mixture was heated to reflux overnight; after the mixture was cooled to room temperature, the solvent was removed by a rotary evaporator, and the crude product was freed from the solvent by a rotary evaporator; the crude product was purified by silica gel flash chromatography using dichloromethane / methanol (v / v, 25:1) as the eluent to obtain yellow solid miCy-OH;

[0018] (3) Synthesis of miCy-Se: A mixture of compounds PhSe (0.3668 g, 1.80 mmol), miCy-OH (0.1549 g, 0.90 mmol), 4-dimethylaminopyridine (0.2199 g, 1.80 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide was dissolved in anhydrous CH2Cl2 and stirred at room temperature overnight; the reaction was completed when detected by TLC, and the mixture was concentrated under reduced pressure. The solid residue was purified by silica gel chromatography (dichloromethane / methanol, v / v, 25:1) to obtain the target compound miCy-Se.

[0019] Application of selenium-containing small molecules loaded with fluorescent groups in anti-tumor drugs.

[0020] Application of selenium-containing small molecules loaded with fluorescent groups as mitochondrial morphology developers.

[0021] The improvement of the present application brings the following advantages: The experimental results of the present invention show that the small molecule has a good killing effect on tumor cells, can specifically target mitochondria, and act as a mitochondrial imaging agent. This small molecule can be used for the integrated diagnosis and treatment of tumor treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 is the ESI-MS mass spectrum of miCy-Se of the present application example;

[0023] Figure 2 is the miCy-Se of the present application example 1 H NMR spectra;

[0024] Figure 3 The infrared spectra of miCy-OH and miCy-Se in the examples of this application are

[0025] Figure 4 The spatial localization function and laser confocal co-localization imaging of miCy-OH and miCy-Se in the embodiment of the present application are as follows: (a) mitochondrial co-localization and (b) lysosomal co-localization. DETAILED DESCRIPTION

[0026] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0027] Example 1: Synthesis of Selenium-containing Small Molecules Loaded with Fluorescent Groups

[0028] Synthesis of PhSe

[0029] 3,4-Diaminobenzoic acid (1.54 g, 10 mmol) and selenium dioxide (1.11 g, 10 mmol) were mixed in aqueous solution, concentrated hydrochloric acid was added dropwise and stirred at room temperature for 2 h. The product was filtered, washed with water and ethanol, and dried in vacuum to obtain compound PhSe.

[0030] Synthesis of miCy-OH

[0031] First, 1,1,2-trimethyl-1H-benzo[e]indole (500 mg, 2.39 mmol) and iodoethane (745 mg, 4.78 mmol) were added to a round-bottom flask containing 10 mL of acetonitrile under nitrogen protection. The mixed solution was stirred and refluxed at 75 ° C. The reaction was monitored by TLC. The solvent was removed by a rotary evaporator, and the crude product was washed with petroleum ether several times to obtain the compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium without purification. The compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium (249 mg, 1.05 mmol) and 6-hydroxy-2-naphthaldehyde (172.2 mg, 1 mmol) were dissolved in 20 mL of EtOH, and then a small amount of piperidine was added dropwise. The mixture was heated at reflux overnight. After the mixture was cooled to room temperature, the solvent was removed by a rotary evaporator, and the crude product was purified by silica gel flash chromatography using dichloromethane / methanol (v / v, 25:1) as eluent to obtain miCy-OH as a yellow solid.

[0032] Synthesis of miCy-Se

[0033] A mixture of compound PhSe (0.3668 g, 1.80 mmol), miCy-OH (0.1549 g, 0.90 mmol), 4-dimethylaminopyridine (0.2199 g, 1.80 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) (0.3452 g, 1.80 mmol) was dissolved in anhydrous CH2Cl2 and stirred at room temperature overnight. The reaction was detected to be complete by TLC, and the mixture was concentrated under reduced pressure. The solid residue was purified by silica gel chromatography (dichloromethane / methanol, v / v, 25:1; i.e., the eluent was a mixed solution of dichloromethane / methanol with a volume ratio of 25:1) to obtain the target compound miCy-Se.

[0034] Example 2: Synthesis of Selenium-containing Small Molecules Loaded with Fluorescent Groups

[0035] Synthesis of PhSe

[0036] 3,4-Diaminobenzoic acid (1.54 g, 10 mmol) and selenium dioxide (1.221 g, 11 mmol) were mixed in aqueous solution, concentrated hydrochloric acid was added dropwise and stirred at room temperature for 2.5 h. The product was filtered, washed with water and ethanol, and dried in vacuum to obtain compound PhSe.

[0037] Synthesis of miCy-OH

[0038] First, 1,1,2-trimethyl-1H-benzo[e]indole (500 mg, 2.39 mmol) and iodoethane (745 mg, 4.78 mmol) were added to a round-bottom flask containing 10 mL of acetonitrile under nitrogen protection. The mixed solution was stirred and refluxed at 75 ° C. The reaction was monitored by TLC. The solvent was removed by a rotary evaporator, and the crude product was washed with petroleum ether several times to obtain the compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium without purification. The compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium (249 mg, 1.05 mmol) and 6-hydroxy-2-naphthaldehyde (172.2 mg, 1 mmol) were dissolved in 20 mL of EtOH, and then a small amount of piperidine was added dropwise. The mixture was heated at reflux overnight. After the mixture was cooled to room temperature, the solvent was removed by a rotary evaporator, and the crude product was purified by silica gel flash chromatography using dichloromethane / methanol (v / v, 25:1) as eluent to obtain miCy-OH as a yellow solid.

[0039] Synthesis of miCy-Se

[0040] A mixture of compound PhSe (0.2934 g, 1.44 mmol), miCy-OH (0.1859 g, 1.08 mmol), 4-dimethylaminopyridine (0.1759 g, 1.44 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) (0.2760 g, 1.44 mmol) was dissolved in anhydrous CH2Cl2 and stirred at room temperature overnight. The reaction was detected to be complete by TLC, and the mixture was concentrated under reduced pressure. The solid residue was purified by silica gel chromatography (dichloromethane / methanol, v / v, 25:1; i.e., the eluent was a mixed solution of dichloromethane / methanol with a volume ratio of 25:1) to obtain the target compound miCy-Se.

[0041] Example 3: Synthesis of Selenium-containing Small Molecules Loaded with Fluorescent Groups

[0042] Synthesis of PhSe

[0043] 3,4-Diaminobenzoic acid (1.54 g, 10 mmol) and selenium dioxide (1.332 g, 12 mmol) were mixed in aqueous solution, concentrated hydrochloric acid was added dropwise and stirred at room temperature for 3 h. The product was filtered, washed with water and ethanol, and dried in vacuum to obtain compound PhSe.

[0044] Synthesis of miCy-OH

[0045] First, 1,1,2-trimethyl-1H-benzo[e]indole (500 mg, 2.39 mmol) and iodoethane (745 mg, 4.78 mmol) were added to a round-bottom flask containing 10 mL of acetonitrile under nitrogen protection. The mixed solution was stirred and refluxed at 75 ° C. The reaction was monitored by TLC. The solvent was removed by a rotary evaporator, and the crude product was washed with petroleum ether several times to obtain the compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium without purification. The compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium (249 mg, 1.05 mmol) and 6-hydroxy-2-naphthaldehyde (172.2 mg, 1 mmol) were dissolved in 20 mL of EtOH, and then a small amount of piperidine was added dropwise. The mixture was heated at reflux overnight. After the mixture was cooled to room temperature, the solvent was removed by a rotary evaporator, and the crude product was purified by silica gel flash chromatography using dichloromethane / methanol (v / v, 25:1) as eluent to obtain miCy-OH as a yellow solid.

[0046] Synthesis of miCy-Se

[0047] A mixture of compound PhSe (0.4402 g, 2.16 mmol), miCy-OH (0.1239 g, 0.72 mmol), 4-dimethylaminopyridine (0.2639 g, 2.16 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) (0.4141 g, 2.16 mmol) was dissolved in anhydrous CH2Cl2 and stirred at room temperature overnight. The reaction was detected to be complete by TLC, and the mixture was concentrated under reduced pressure. The solid residue was purified by silica gel chromatography (dichloromethane / methanol, v / v, 25:1; i.e., the eluent was a mixed solution of dichloromethane / methanol with a volume ratio of 25:1) to obtain the target compound miCy-Se.

[0048] Experiment 4: Characterization of Selenium-containing Small Molecules Loaded with Fluorophores

[0049] (1) Mass spectrometry

[0050] Take a small amount of sample (miCy-Se) and dissolve it in HPLC methanol, then filter it with a 0.22μM filter head, and collect mass spectrometry data of the complex solution in positive ion mode. Figure 1 .ESI-HRMS(m / z):602.1341[C 35 H 28 N3O2Se]+, found 302.1336. The results indicated the successful synthesis of the compound.

[0051] (2) NMR

[0052] The compound was dissolved in deuterated dimethyl sulfoxide and the hydrogen spectrum of the compound was detected by 300 MHz NMR. Figure 2 As shown, 1 HNMR (300MHz, DMSO-d6)δ8.87(s,1H),8.79(s,2H),8.53–8.46(m,2H),8.34(d,J=9.0Hz,1H),8.29–8.14(m,5H),8.09(dd,J=5.5,3.2Hz,2H),7.93–7.81(m,2H),7.80–7.69(m,2H),4.93(d,J=7.2Hz,2H),2.11(s,6H),1.59(t,J=7.2Hz,3H). The results showed that the compound miCy-Se was successfully synthesized.

[0053] (3) Infrared

[0054] Take a small amount of powder and test it in infrared spectrometer, such as Figure 3As shown. The strong absorption peak of C=O of ester appears at 1735-1750cm-1 and the absorption peak of CO appears at 1000-1300cm-1, which proves the successful synthesis of ester bond. Experiment 5: Study on the anti-tumor activity of selenium-containing small molecules loaded with fluorescent groups in vitro

[0055] The method of measuring the growth inhibition of tumor cells (4T1, MDA-MB-231, HeLa, Siha, MCF-7 cells) and normal cells (H9C, Wi38) by miCy-Se in Experiment 1 using the MTT method mainly includes the following steps:

[0056] (1) Dissolve miCy-Se in DMSO (dimethyl sulfoxide), place it on an ultrasonicator and sonicate for 1 to 2 minutes to prepare a 5 mmol / L solution for later use;

[0057] (2) Different tumor cells and normal cells in logarithmic growth phase (American Model Culture Collection) were collected at a density of 2×10 4 cells / mL were inoculated into a 96-well plate (100 μL / well) and allowed to adhere to the wall and grow for 24 hours. Then, 100 μL of the drugs in different concentrations in step (1) were added respectively and cultured for another 72 hours. After the cells showed a certain degree of damage, 30 μL of MTT solution (5 mg / mL, PBS solution) was added to each well and incubated for 3 hours. Next, the upper culture medium (DMEM high-glucose medium, Gibco) in the 96-well plate was removed, and 150 μL DMSO (dimethyl sulfoxide) was added. The plate was gently shaken on a shaker for 15 minutes to fully dissolve the purple crystals in the 96-well plate. The absorbance of each well at 570 nm was then measured using a multifunctional microplate reader, and the cell survival rate was calculated. At the same time, a graph was drawn to obtain the half inhibitory concentration (IC 50 Cell survival rate (%) = (OD 570 Experimental group / OD 570 Control group)×100%.

[0058] Test results:

[0059] As shown in Table 1, miCy-Se has a significant inhibitory effect on most cancer cells and is highly toxic to cancer cells, especially MDA-MB-231 cells, but has a low toxicity to normal cells. The drug shows high selectivity for cancer cells and normal cells, and also shows very high selectivity for MDA-MB-231 and MCF-7 cells, which have different metastatic and invasive properties of human cancer cells tested. Therefore, miCy-Se has a strong research value for the treatment of cancer.

[0060] Table 1 MTT toxicity test results of miCy-Se on tumor cells and normal cells

[0061]

[0062]

[0063] Experiment 6: Spatial localization and fluorescence imaging of selenium-containing small molecules loaded with fluorescent groups in cells

[0064] Confocal co-localization imaging was used to explore the spatial localization and fluorescence imaging of miCy-Se in cells. The steps are as follows:

[0065] MDA-MB-231 cells were seeded in a laser confocal dish for 24 hours to adhere to the wall, and then incubated with mitochondrial localization dye (mito tracker Deep Red) and lysosomal localization dye (Lyso tracker green) for 30 minutes. After washing with PBS, they were incubated with miCy-Se for another 30 minutes. After washing with PBS, the cells were immediately photographed using a confocal microscope (LSM 710, Carl Zeiss, G€ottingen, Germany).

[0066] Test results:

[0067] like Figure 4 After miCy-Se was co-treated with commercial specific mitochondrial deep red emission probe (MitoTracker Deep Red) and commercial specific lysosomal green emission probe (LysoTracker Green) in living cells, the intensity change curves of the bright red light emission after miCy-OH and miCy-Se treatment of cells and the purple fluorescence of MitoTracker Deep Red were consistent, indicating that miCy-Se has the ability to target mitochondria. At the same time, clear tubular mitochondria were observed in the miCy-Se image. However, the co-localization fluorescence intensity change curves of miCy-Se and commercial specific lysosomal green emission probe (LysoTracker Green DND-26) were less similar, indicating that miCy-Se did not have the ability to target lysosomes. These results prove that miCy-Se can specifically target mitochondria and can be used as a developer of mitochondrial morphology.

[0068] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A selenium-containing small molecule loaded with a fluorescent group, characterized in that: Prepared by the following reaction formula:

2. The method for preparing the selenium-containing small molecule loaded with fluorescent groups according to claim 1, characterized in that: The following steps are involved: (1) Synthesis of PhSe; (2) Synthesis of miCy-OH; (3) Synthesis of miCy-Se: A mixture of compounds PhSe, miCy-OH, 4-dimethylaminopyridine and 1-ethyl-(3-dimethylaminopropyl)carbodiimide was dissolved in anhydrous CH2Cl2 and stirred at room temperature overnight. The reaction was completed by TLC, and the mixture was concentrated under reduced pressure. The solid residue was purified by silica gel chromatography to obtain the target compound miCy-Se.

3. The preparation method according to claim 2, characterized in that: In step (3), a mixture of 0.8-1.2 parts of compound PhSe, 0.4-0.6 parts of miCy-OH, 0.8-1.2 parts of 4-dimethylaminopyridine and 0.8-1.2 parts of 1-ethyl-(3-dimethylaminopropyl)carbodiimide is dissolved in anhydrous CH2Cl2 and stirred at room temperature overnight; the above-mentioned amounts are based on the amount of substance.

4. The preparation method according to claim 2, characterized in that: The step (1) specifically comprises: mixing 3,4-diaminobenzoic acid and selenium dioxide in an aqueous solution, adding concentrated hydrochloric acid dropwise and stirring at room temperature, filtering the product, washing with water and ethanol, and vacuum drying to obtain compound PhSe.

5. The preparation method according to claim 4, characterized in that: In the step (1), the molar ratio of 3,4-diaminobenzoic acid to selenium dioxide is 1:1 to 1-1.

2.

6. The preparation method according to claim 2, characterized in that: The step (2) specifically comprises: first, adding 1,1,2-trimethyl-1H-benzo[e]indole and iodoethane to a round-bottom flask containing acetonitrile under nitrogen protection; stirring and refluxing the mixed solution at a certain temperature; removing the solvent by a rotary evaporator, and washing the crude product with petroleum ether for multiple times to obtain the compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium; dissolving the compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indole-3-ium and 6-hydroxy-2-naphthaldehyde in EtOH, and then dropping a small amount of piperidine; heating the mixture to reflux overnight; after cooling the mixture to room temperature, removing the solvent by a rotary evaporator, and removing the solvent from the crude product by a rotary evaporator; purifying the crude product by silica gel flash chromatography using dichloromethane / methanol as an eluent to obtain a yellow solid miCy-OH.

7. The preparation method according to any one of claims 2 to 6, characterized in that: The following steps are involved: (1) Synthesis of PhSe: 3,4-diaminobenzoic acid (1.54 g, 10 mmol) and selenium dioxide (1.11 g, 10 mmol) were mixed in an aqueous solution, concentrated hydrochloric acid was added dropwise and stirred at room temperature for 2 h; the product was filtered, washed with water and ethanol, and dried in vacuum to obtain compound PhSe; (2) Synthesis of miCy-OH: First, 1,1,2-trimethyl-1H-benzo[e]indole (500 mg, 2.39 mmol) and iodoethane (745 mg, 4.78 mmol) were added to a round-bottom flask containing 10 mL of acetonitrile under nitrogen protection; the mixed solution was stirred and refluxed at 75°C, and the reaction was monitored by TLC; the solvent was removed by a rotary evaporator, and the crude product was washed with petroleum ether several times to obtain compound 3-ethyl-1,1,2-trimethyl-1H-benzo[e]indol-3-ium without purification; compound 3- Ethyl-1,1,2-trimethyl-1H-benzo[e]indol-3-ium (249 mg, 1.05 mmol) and 6-hydroxy-2-naphthaldehyde (172.2 mg, 1 mmol) were dissolved in 20 mL of EtOH, and then a small amount of piperidine was added dropwise; the mixture was heated to reflux overnight; after the mixture was cooled to room temperature, the solvent was removed by a rotary evaporator, and the crude product was freed of the solvent by a rotary evaporator; the crude product was purified by silica gel flash chromatography using dichloromethane / methanol (v / v, 25:1) as the eluent to obtain yellow solid miCy-OH; (3) Synthesis of miCy-Se: A mixture of compounds PhSe (0.3668 g, 1.80 mmol), miCy-OH (0.1549 g, 0.90 mmol), 4-dimethylaminopyridine (0.2199 g, 1.80 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide (0.2760 g, 1.44 mmol) was dissolved in anhydrous CH2Cl2 and stirred at room temperature overnight; the reaction was completed when detected by TLC, and the mixture was concentrated under reduced pressure. The solid residue was purified by silica gel chromatography (dichloromethane / methanol, v / v, 25:1) to obtain the target compound miCy-Se.

8. Use of the selenium-containing small molecule loaded with fluorescent group according to claim 1 in anti-tumor drugs.

9. Use of the selenium-containing small molecule loaded with fluorescent group as claimed in claim 1 in a mitochondrial morphology developer.

Images