A kind of fluorescent compound of β-carbolinium salt for mitochondrial targeting and photodynamic therapy and its preparation method and application

A fluorescent compound and photodynamic therapy technology, applied in the field of biomedicine, can solve the problem of lack of integrated strategy of tumor cell diagnosis and treatment, and achieve the effect of low dark toxicity, broad application and good mitochondrial targeting.

Active Publication Date: 2021-11-12
NANTONG UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, most of the current research focuses on the changes in the overall environment of cells during treatment, and there is a lack of integrated strategies for tumor cell diagnosis and treatment based on mitochondrial targeting.

Method used

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  • A kind of fluorescent compound of β-carbolinium salt for mitochondrial targeting and photodynamic therapy and its preparation method and application
  • A kind of fluorescent compound of β-carbolinium salt for mitochondrial targeting and photodynamic therapy and its preparation method and application
  • A kind of fluorescent compound of β-carbolinium salt for mitochondrial targeting and photodynamic therapy and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1: (E)-4-(2-(1,9-Dimethyl-9H-pyrido[3,4-b]indol-3-yl)vinyl)-1-methylquinoline -1-Iodine salt (I 1 ) preparation;

[0040]

[0041] 1,9-Dimethyl-9H-pyrido[3,4-b]indole-3-carbaldehyde (2.24g, 10mmol) and 1,4-dimethylquinoline-1-iodide (2.85g , 10mmol) into a single-necked bottle, add 5ml of absolute ethanol, then add 1 drop of piperidine, reflux overnight, TLC monitors the reaction until complete, the reaction solution is cooled and filtered, and recrystallized and purified again to obtain a red solid (I 1 )4.2g, the yield was 85.7%. (I 1 ) The spectrum data is: ESI-MS(m / z):492[M+H] + ; 1 HNMR(d 6 -DMSO, 400MHz): δ9.29(d, J=6.5Hz, 1H, Ar-H), 8.86(d, J=8.5Hz, 1H, Ar-H), 8.59(s, 1H, Ar-H) ,8.56–8.37(m,3H,Ar-H,CH),8.34–8.20(m,3H,Ar-H,CH),8.12–8.04(m,1H,Ar-H),7.77(d,J= 8.4Hz,1H,Ar-H),7.72–7.63 (m,1H,Ar-H),7.38–7.34(m,1H,Ar-H),4.50(s,3H,CH 3 ),4.20(s,3H,CH 3 ),3.15(s,3H,CH 3 ).

Embodiment 2

[0042] Example 2: (E)-4-(2-(1,9-dimethyl-9H-pyrido[3,4-b]indol-3-yl)ethenyl)-1-(butan-3 -Alkyn-1-yl)quinoline-1-methanesulfonate (I 2 ) preparation;

[0043] With reference to (I in embodiment 1 1 ) synthetic method, 1,4-dimethylquinoline-1-iodine in the method is replaced by 4-methyl-1-(but-3-yn-1-yl) quinoline-1-methanesulfonate salt, and finally a reddish-brown solid (I 2 )3.9g, the yield was 79.6%. (I 2 ) spectrogram data is: ESI-MS (m / z): 498[M+H] + ; 1 HNMR(d 6 -DMSO, 400MHz): δ9.31(d, J=6.6Hz, 1H, Ar-H), 8.89 (d, J=8.6Hz, 1H, Ar-H), 8.58(s, 1H, Ar-H) ,8.58–8.41(m,3H,Ar-H,CH),8.37–8.25(m,3H,Ar-H,CH),8.15–8.07(m,1H,Ar-H),7.80(d,J= 8.4Hz,1H,Ar-H),7.71–7.64(m,1H,Ar-H), 7.42–7.34(m,1H,Ar-H),4.69–4.61(m,2H,CH 2 ),4.26(s,3H,CH 3 ),3.17(s,3H,CH 3 ), 2.14(s, 1H, CH), 2.10–2.04(m, 2H, CH 2 ).

Embodiment 3

[0044] Example 3: (E)-4-(2-(9-(2-ethyl)-1-methyl-9H-pyrido[3,4-b]indol-3-yl)ethenyl)- 1-methylquinoline-1-iodide salt (I 3 ) preparation;

[0045] With reference to (I in embodiment 1 1 ) synthetic method, the 1,9-dimethyl-9H-pyrido[ 3,4-b] indole-3-carbaldehyde, finally obtained red solid (I 3 )4.7g, the yield is 80.5%. (I 3 ) spectrum data is: ESI-MS (m / z): 506[M+H] + ; 1 HNMR(d 6 -DMSO,400MHz):δ9.28(s,1H,Ar-H), 8.85(d,J=8.4Hz,1H,Ar-H),8.57(s,1H,Ar-H),8.54–8.39( m,3H,Ar-H,CH),8.33–8.23(m,3H,Ar-H,CH),8.13–8.05(m,1H,Ar-H),7.73(d,J=8.4Hz,1H, Ar-H),7.70–7.62(m,1H,Ar-H),7.32–7.29(m,1H,Ar-H),4.53(s,3H,CH 3 ),4.25–4.17(m,2H,CH 2 ),3.16(s,3H,CH 3 ), 2.72–2.59 (m,3H,CH 3 ).

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Abstract

The present invention relates to the technical field of biomedicine, in particular to a fluorescent compound of a β-carbolinium salt for mitochondrial targeting and photodynamic therapy and its preparation method and application. It has the structure shown in general formula I: the present invention is based on β-carboline The tricyclic planar skeleton structure of indolopyridine, which is the parent ring of the alkaloid, uses its strong electron donating ability, better rigidity and conjugation system to introduce an aldehyde group at the 3-position of β-carboline, and replace it with methyl Lipophilic cations such as quinolinium salts or naphthyridinium salts undergo aldol condensation reactions to obtain a class of β-carbolinium salt fluorescent compounds with mitochondrial targeting and photodynamic therapy effects. The compound itself has low dark toxicity, photodynamic therapy effect, etc., and is also suitable for mitochondria-targeted fluorescent probes, which can preferentially target tumor tissues and cells, so as to perform in vivo and in vitro tumor fluorescence diagnostic imaging, and at specific wavelengths Singlet oxygen is generated after light irradiation, thereby effectively killing tumor cells, and can be used for the integration of tumor diagnosis and treatment.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a fluorescent compound of β-carbolinium salt for mitochondrial targeting and photodynamic therapy, a preparation method and application thereof. Background technique [0002] The occurrence and development of cancer is a complex biological process involving multiple signaling pathways and multiple genes. Compared with normal cells, tumor cells have the characteristics of unlimited proliferation, tissue metastasis, and abnormal energy metabolism. Therefore, a new strategy for cancer therapy targeting mitochondria is proposed. As we all know, mitochondria are the "power factory" of eukaryotic cell material and energy metabolism, and are closely related to the occurrence and development of tumors. However, the mechanism of mitochondrial action in cancer cells has not been fully elucidated yet. The common targeting groups of tumor cell mitochondria are lipophilic cations. The pr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/04C07D519/00C09K11/06G01N21/64A61K49/00A61K41/00A61P35/00
CPCA61K41/0057A61K49/0021A61P35/00C07D471/04C07D519/00C09K11/06C09K2211/1029C09K2211/1044G01N21/6428
Inventor 凌勇刘季钱建强孟迟邱晓东刘昕冉凡胜张延安单文配徐思源
Owner NANTONG UNIVERSITY
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