Substituted indole-2-carboxylic acid Bcl-2 small-molecule fluorescent probe and application thereof

A fluorescent probe, bcl-2 technology, applied in fluorescence/phosphorescence, luminescent materials, analytical materials, etc., can solve the problems of lack of design and synthesis methods, and few small molecule probes

Active Publication Date: 2018-07-06
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few small-molecule probes that can specifically bind to target proteins, and the lack of design and synthesis methods

Method used

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  • Substituted indole-2-carboxylic acid Bcl-2 small-molecule fluorescent probe and application thereof
  • Substituted indole-2-carboxylic acid Bcl-2 small-molecule fluorescent probe and application thereof
  • Substituted indole-2-carboxylic acid Bcl-2 small-molecule fluorescent probe and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0118] The measurement of embodiment 1 optical activity

[0119] Table 1: Optical characteristics of probe molecules

[0120]

[0121] Note: All the above optical properties were measured in phosphate buffer at pH=7.4.

Embodiment 2

[0122] Embodiment 2: the mensuration of biological activity

[0123] Using gossypol (Gossypol) as a positive drug, FP or TR-FRET experiments were used to measure the binding activity of fluorescent probe molecules to Bcl-2 family proteins, and the results are shown in Table 2. The activities of the synthesized probe molecules L1, L3 and L3 were equivalent to those of the positive control gossypol, and the activity of the probe L4 was lower than that of the positive control gossypol.

[0124] Table 2: Affinity of probe molecules to Bcl-2 family proteins

[0125]

Embodiment 3

[0126] Example 3: Application of probe molecules in imaging HEK293 cells with high and low expression of Bcl-2

[0127] Probe molecules L1 and L3-L4 were used as research objects to investigate their application in cell imaging. Hela cells were selected as positive cells and HEK293 as negative cells. Under the same conditions, the inhibitor gossypol was added as a negative control. The specific steps are: Hela cells and HEK293 cells use DMEM medium containing 10% fetal bovine serum; 2 Culture in air and at 37°C. Before imaging, inoculate the cells in confocal small dishes, culture for 12-24 hours, suck off the medium, wash once with serum-free medium, and add probes L1-L4 respectively (Prepared in serum-free medium, the concentration is 1 μM); under the same conditions, another small dish was added with probes L1-L4 and inhibitor gossypol (prepared in serum-free medium, the concentration of L1 and L3 was 10 μM, gossypol Concentration of 10 μM; L4 concentration of 5 μM, gossyp...

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Abstract

The invention discloses a substituted indole-2-carboxylic acid Bcl-2 small-molecule fluorescent probe and application thereof. Structural general formulas of the fluorescent probe is shown as follows:a general formula I and a general formula II are shown in the description; in the general formula I, R1 is each fluorescent group; R2 is halogen; in the general formula II, R3 is each fluorescent group; R4 is halogen. The small-molecule fluorescent probe can be used as a probe for identifying Bcl-2 family protein and used for researching physiology, pathology and related diseases related to Bcl-2; the small-molecule fluorescent probe can be used for high-flux screening of a Bcl-2 inhibitor and anti-tumor aspects, and also can be used for marking the Bcl-2 family protein and tumor cells or tissues which are highly expressed by the Bcl-2 family protein. Furthermore, a preparation method of the compound has the advantages of moderate reaction conditions, cheap and easy-to-obtain raw materials and simplicity in operation and post-treatment.

Description

technical field [0001] The invention relates to a substituted indole-2-carboxylic acid derivative and its use as a Bcl-2 small molecule fluorescent probe, and its application in Bcl-2 inhibitor activity screening, cytotoxicity evaluation and cell imaging, belonging to the technical field of medicines. Background technique [0002] B-cell lymphoma / leukemia-2 (B-cell leukemia / lymphoma-2, Bcl-2) protein family is an important regulatory factor in the endogenous pathway of apoptosis, and plays an important regulatory role in the apoptosis pathway . According to the difference in structure and function, the Bcl-2 protein family can be divided into anti-apoptotic family proteins and pro-apoptotic family proteins. In normal cells, the heterodimerization of pro-apoptotic family proteins and anti-apoptotic family proteins keeps the cells in a normal growth state, avoiding premature apoptosis of cells and preventing cells from transforming into tumor cells due to non-apoptosis . Ho...

Claims

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Application Information

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IPC IPC(8): C09K11/06C07D209/42C07D403/12G01N21/64
CPCC07D209/42C07D403/12C09K11/06C09K2211/1007C09K2211/1011C09K2211/1029C09K2211/1059G01N21/6486
Inventor 李敏勇杜吕佩刘婷婷
Owner SHANDONG UNIV
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