Synthesis of benzenesulfonamide phenylbutyric acid podophyllotoxin ester derivatives and application of benzenesulfonamide phenylbutyric acid podophyllotoxin ester derivatives in anti-cancer drugs

A technology of benzenesulfonamide phenylbutyric acid and podophyllotoxin, which is applied in the field of preparation of benzenesulfonamide phenylbutyric acid podophyllotoxin carboxylate derivatives, can solve problems such as toxic and side effects, limit clinical use and the like, and achieve toxic and side effects Low, obvious tumor cell inhibitory activity, strong inhibitory activity effect

Active Publication Date: 2021-08-06
济宁市第一人民医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Etoposide and teniposide are the two main semi-synthetic glycosyl derivatives of podophyllotoxin, which have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of various

Method used

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  • Synthesis of benzenesulfonamide phenylbutyric acid podophyllotoxin ester derivatives and application of benzenesulfonamide phenylbutyric acid podophyllotoxin ester derivatives in anti-cancer drugs
  • Synthesis of benzenesulfonamide phenylbutyric acid podophyllotoxin ester derivatives and application of benzenesulfonamide phenylbutyric acid podophyllotoxin ester derivatives in anti-cancer drugs
  • Synthesis of benzenesulfonamide phenylbutyric acid podophyllotoxin ester derivatives and application of benzenesulfonamide phenylbutyric acid podophyllotoxin ester derivatives in anti-cancer drugs

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Experimental program
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Effect test

example 1

[0025] Example 1: Preparation of Formula I Benzenesulfonamide Benzenebutyrate Podophyllotoxin Ester Derivatives

[0026] Dissolve 5.58 mmol of p-aminophenylbutyric acid in 20 mL of water, stir at room temperature, adjust the pH to 8-9 with saturated sodium carbonate solution, and continue stirring until the acid is completely dissolved in the water. To the reaction system, 6 mmol of benzenesulfonyl chloride containing different substituents was added, and the mixture was stirred at room temperature overnight. After the reaction finishes, dropwise add the hydrochloric acid solution with a concentration of 1 mol / L to the reaction system to a pH of 1~2, separate out a large amount of solid, then use a Buchner funnel through vacuum filtration, wash with water, and dry the light yellow obtained. Solid, the intermediate product benzenesulfonamide phenylacetic acid derivative is obtained. This product can be used directly in the next chemical synthesis, or it can be further purified...

example 2

[0045] Example 2: Application of Formula I Benzenesulfonamide Benzenebutyrate Podophyllotoxin Ester Derivatives

[0046] MCF-7, HeLa, H460, A549 and L02 human normal liver cell lines were used as detection strains, and MTT colorimetry was used as detection method. The inhibitory activity study found that the novel structural derivatives have obvious tumor cell inhibitory activity in vitro. The results are attached figure 1 , 2 , 3, 4.

example 3

[0047] Example 3: Compound 5z significantly induces apoptosis

[0048] Different concentrations (0, 0.5, 1, 2 μM) of compound 5z and PPT (2 μM) acted on A549 cells respectively, treated for 24 h, collected cells, centrifuged, and washed cells twice with PBS; The cells were resuspended in bindingbuffer, 5 μL of FITC and 10 μL of LPI were added, and the cells were stained in the dark for 15 minutes, and cell apoptosis was detected by flow cytometry. The results are attached Image 6 . The derivatives of this novel structure can obviously promote the apoptosis of human non-small cell lung cancer cell A549.

[0049] The benzenesulfonamide phenylbutyrate podophyllotoxin ester derivatives of the present invention can be prepared into antitumor drugs.

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Abstract

The invention discloses benzenesulfonamide phenylbutyric acid podophyllotoxin carboxylic ester derivatives as well as a synthesis method and application thereof, belongs to the technical field of chemical pharmacy. The invention particularly relates to podophyllotoxin derivatives and application thereof in tumor inhibition. Corresponding benzene sulfonamide phenylbutyric acid is connected with podophyllotoxin through a synthesis means to obtain corresponding ester derivatives, and in-vitro anti-tumor activity research shows that the podophyllotoxin carboxylic ester derivatives have very strong inhibitory activity on tumor cell strains.

Description

[0001] 1. Technical field [0002] The invention belongs to the technical field of chemical pharmacy, and in particular relates to the preparation of a class of benzenesulfonamide phenylbutyrate podophyllotoxin carboxylate derivatives and its application in tumor inhibition. [0003] 2. Background technology [0004] Podophyllotoxin is a natural anti-tumor active ingredient with significant cytotoxicity, which is mainly derived from Berberis podophyllum plants, because it also has significant antibacterial, antirheumatic, antiparasitic and antiviral pharmacological Active and widely concerned by scholars at home and abroad. Etoposide and teniposide, the two main semisynthetic glycosyl derivatives of podophyllotoxins, have been approved by the US Food and Drug Administration (FDA) for the treatment of various types of cancer. Toxic side effects such as myelosuppression, alopecia, and neurotoxicity frequently occur in clinical treatment, which greatly limit their clinical use. ...

Claims

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Application Information

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IPC IPC(8): C07D493/04A61P35/00
CPCC07D493/04A61P35/00
Inventor 江沛孙文学崔昌萌刘蒙蒙赵世媛王长水
Owner 济宁市第一人民医院
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