Mitochondrion-targeted heptamethine indocyanine dye, preparation method and application

A technology of heptamethine indole cyanine and mitochondria, applied in the direction of methine/polymethine dyes, organic dyes, chemical instruments and methods, etc.

Active Publication Date: 2016-05-11
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, synergistic therapy of mitochondrial-targeted PDT and PTT has not been reported

Method used

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  • Mitochondrion-targeted heptamethine indocyanine dye, preparation method and application
  • Mitochondrion-targeted heptamethine indocyanine dye, preparation method and application
  • Mitochondrion-targeted heptamethine indocyanine dye, preparation method and application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Synthesis of Compound A0

[0055] A solution of 35 mL of dry dichloromethane and 37 mL of phosphorus oxychloride was dropped into a mixture of 80 mL of dry dichloromethane and N,N-dimethylformyl (1:1, v / v) under an ice bath. Maintaining at 0°C, 10 g (0.10 mol) of cyclohexanone was added dropwise to the reaction solution, and then the temperature was slowly raised to reflux for 3 h. Stop the reaction, cool in an ice-water bath, and pour the reaction solution into 200 g of crushed ice in batches. A large amount of red solid precipitated out. Filter under reduced pressure, wash the solid in batches with frozen acetone until yellow, and vacuum-dry to obtain a crude product, which is recrystallized from acetone to obtain 12.86 g of a yellow solid (compound A0), yield: 73%, melting point: 130-132°C.

Embodiment 2

[0057] Preparation of Compounds A1-A6:

[0058]

[0059] Take 3.84g (2.41×10 -2 mol)2,3,3-trimethyl-3H-indole in a 100ml single-necked round bottom bottle, add 2.89×10 -2 mol of each brominated organic compound, add 30ml of toluene, react at 110°C for 12h, take a sample and monitor the reaction by TLC (dichloromethane:methanol=15:1), it shows that the reaction of the raw materials is complete, and the toluene is removed by rotary evaporation to obtain a reddish-brown viscous liquid. Roughly recrystallized with dichloromethane-ether to obtain reddish-brown viscous liquids A1-A6. The product was directly subjected to the next reaction without purification.

Embodiment 3

[0061] Preparation of Compound 1-6:

[0062]

[0063] Take 7.75×10 -3 molA1-A6 was added to a 100ml single-mouth round bottom bottle, and 0.67g (3.87×10 -3 mol) A0, add 0.66g (7.75×10 -3 mol) sodium acetate, add 40ml acetic anhydride, stir, react at 70°C for 1h, take a sample TLC to monitor the reaction (dichloromethane:methanol=15:1), it shows that the reaction of raw materials is complete, transfer the reaction solution to a separatory funnel, and use Wash with saturated NaCl solution, anhydrous NaSO 4 Dry, filter, and concentrate under reduced pressure to obtain a reddish-brown liquid, roughly recrystallized with dichloromethane-ether to obtain a reddish-brown solid, and column chromatography to obtain a dark green solid compound 1-6:

[0064] 1 (11%): 1 HNMR (400Hz, DMSO-d 6 )δ: 8.26(d, J=14.4Hz, 2H), 7.94(d, J=8.0Hz, 4H), 7.69(d, J=7.6Hz, 2H), 7.40(t, J=7.2Hz, 8H) ,7.33-7.28(m,2H),6.38(d,J=14.0Hz,2H),5.63(s,4H),2.53-2.50(m,4H),1.73(s,14H); HRMS[M-Br ] + :calc.7...

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Abstract

The invention relates to a mitochondrion-targeted heptamethine indocyanine dye, a preparation method and application. The mitochondrion-targeted heptamethine indocyanine dye is composed of a mitochondrion-targeted indoheptamethine chain and N-alkyl side chains of different lengths. The mitochondrion-targeted heptamethine indocyanine dye is multifunctional small organic molecules which are guided by near infrared fluorescence imaging to synchronously achieve the precise and efficient photothermal and photodynamic anti-tumor effect by taking a tumor mitochondrion as a target. The mitochondrion-targeted heptamethine indocyanine dye provides feasibility for thorough inhibition on tumor growth and prevention on drug resistance and relapse. A photosensitizer prepared from the mitochondrion-targeted heptamethine indocyanine dye better has the application and conversion prospect compared with an existing relying nanomaterail photosensitizer which is expensive and complex in preparation.

Description

technical field [0001] The invention relates to the field of biology, in particular to a class of mitochondria-targeted heptamethine indole cyanine dyes, a preparation method and application thereof. Background technique [0002] Malignant tumor is a major disease that seriously endangers human health and life, and has become the number one cause of death in my country. Drug resistance and recurrence of tumors are important reasons why tumors are difficult to overcome. At present, it is believed that improving the targeting of drugs and combining multiple treatments is an important way to reduce tumor drug resistance and recurrence. Tumor phototherapy has always been considered as a local, non-invasive means of treating tumors. Because it only has a therapeutic effect on the local parts treated with light, it is expected to increase the selectivity of treatment and reduce the side effects. Optical therapy for tumors mainly includes two main methods: photodynamic therapy (...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C09B23/08A61K41/00A61K47/22A61P35/00
CPCA61K41/0057A61K47/22C09B23/0016C09B23/0066C09B23/086
Inventor 史春梦罗圣霖谭旭齐庆蓉
Owner ARMY MEDICAL UNIV
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