Cyclopentane polyhydrophenanthrene skeleton compound with anti-tumor effect by regulating blood coagulation factor VIII level and use thereof

A skeleton compound and compound technology, applied in antineoplastic drugs, steroids, organic chemistry, etc., to achieve the effect of inhibiting lung metastasis, high economic efficiency, simple structure and synthesis process

Active Publication Date: 2021-11-16
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

However, no studies have shown that the cyclopentane polyhydrophenanthrene skeleton compound diosgenin and its derivatives can play an anti-hepatic effect by regulating the level of FVIII in vivo
[0003] However, there is no research so far from the perspective of the blood coagulation system. Studies have shown that a cyclopentane polyhydrophenanthrene skeleton compound can play an anti-hepatic effect by regulating FVIII factors. This study is the first to systematically evaluate cyclopentane polyhydrophenanthrene in vitro and in vivo The effect and mechanism of the skeleton compound on the proliferation and migration of liver cancer cells mediated by blood coagulation factor FVIII, providing new research directions and data support for the diagnosis, treatment and drug development of liver cancer

Method used

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  • Cyclopentane polyhydrophenanthrene skeleton compound with anti-tumor effect by regulating blood coagulation factor VIII level and use thereof
  • Cyclopentane polyhydrophenanthrene skeleton compound with anti-tumor effect by regulating blood coagulation factor VIII level and use thereof
  • Cyclopentane polyhydrophenanthrene skeleton compound with anti-tumor effect by regulating blood coagulation factor VIII level and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] In this example, 3-acetylfurostane ester compounds were synthesized, specifically compounds 4-7 were synthesized.

[0043] 1. Synthesis of compound 4: 3-acetyl-aspirin furostanyl ester

[0044] Compound 3 (459mg, 1mmol), aspirin (216mg, 1.2mmol) and 4-dimethylaminopyridine (DMAP, 24mg, 0.2mmol) were dissolved in anhydrous dichloromethane (30mL) and stirred for 10min to form solution A. 1-Ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl, 383mg, 2mmol) was dissolved in 8mL of anhydrous dichloromethane to form solution B, at room temperature Solution B was slowly added dropwise to solution A, and the temperature was gradually raised to 35-40°C for about 8 hours. The reaction progress was detected by TCL, and the reaction was basically complete. The resulting reaction solution was washed successively with 5% sodium chloride solution, saturated sodium bicarbonate solution and 5% sodium chloride solution, the organic phase was separated and dried with anhydr...

Embodiment 2

[0056] In this example, furostane diester compounds were synthesized, specifically including compounds 9-12.

[0057] 1. Synthesis of compound 9: aspirin furostane diester

[0058] Compound 8 (416mg, 1mmol), aspirin (432mg, 2.4mmol) and DMAP (48mg, 0.4mmol) were dissolved in anhydrous dichloromethane (30mL) and stirred for 10min to form solution A, EDC.HCl (766mg, 4mmol ) was dissolved in 8 mL of anhydrous dichloromethane to form solution B, and solution A was slowly added dropwise to solution B at room temperature, and the temperature was gradually raised to 35-40°C for about 8 hours. The reaction progress was detected by TCL, and the reaction was basically complete. The resulting reaction solution was washed successively with 5% sodium chloride solution, saturated sodium bicarbonate solution and 5% sodium chloride solution, the organic phase was separated and dried with anhydrous sodium sulfate, and then washed with petroleum ether:ethyl acetate=10:1( v / v) As an eluent, it ...

Embodiment 3

[0070] In this example, spirostanoid ester compounds were synthesized, specifically including compounds 13-16.

[0071] 1. Synthesis of compound 13: aspirin spirostanyl ester

[0072] Compound 1 (414mg, 1mmol), aspirin (216mg, 1.2mmol) and DMAP (24mg, 0.2mmol) were dissolved in anhydrous dichloromethane (30mL) and stirred for 10min to form solution A, EDC.HCl (383mg, 2mmol ) was dissolved in 5 mL of anhydrous dichloromethane to form solution B, and solution B was slowly added dropwise to solution A at room temperature, and the temperature was gradually raised to 35-40°C for about 8 hours. The reaction progress was detected by TCL, and the reaction was basically complete. The resulting reaction solution was washed successively with 5% sodium chloride solution, saturated sodium bicarbonate solution, and 5% sodium chloride solution, and the organic phase was separated and dried with anhydrous sodium sulfate, and then washed with petroleum ether:ethyl acetate=10:1( v / v) used as e...

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Abstract

The present invention provides a cyclopentane polyhydrophenanthrene skeleton compound which can regulate blood coagulation factor VIII level to exert an anti-tumor effect, and the cyclopentane polyhydrophenanthrene skeleton compound is used in the preparation of drugs for treating tumors mediated by blood coagulation factor VIII, especially It is an application of the medicine for treating tumors mediated by blood coagulation factor VIII and liver cancer mediated by blood coagulation factor VIII. The present invention proves through experiments that the cyclopentane polyhydrophenanthrene skeleton compound can inhibit the expression and secretion of FVIII in HUVEC endothelial cells, inhibit the proliferation of liver cancer cells mediated by FVIII in HUVEC endothelial cells, and inhibit the tumor growth mediated by the secretion of FVIII in HUVEC cells. Cells and platelets adhere, and in vivo experiments have confirmed that the cyclopentane polyhydrophenanthrene skeleton compound inhibits the lung metastasis of liver cancer by inhibiting the level of FVIII.

Description

technical field [0001] The invention belongs to the field of medicines, and relates to a cyclopentane polyhydrophenanthrene skeleton compound capable of regulating the level of blood coagulation factor VIII to exert an antitumor effect and its application. Background technique [0002] Traditional anti-tumor drugs mainly achieve anti-tumor effects by directly killing and injuring cancer cells, with many side effects, and most drugs cannot improve the abnormal function of the blood coagulation system caused by tumors. Studies have shown that the cyclopentane polyhydrophenanthrene skeleton compound dioscin and its derivatives can play the role of anti-venous and arterial thrombosis by regulating the level of coagulation factor VIII (FVIII) in the body, and also found that dioscin and its derivatives have Direct antitumor activity. However, no studies have shown that the cyclopentane polyhydrophenanthrene skeleton compound diosgenin and its derivatives can play an anti-hepatic...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J71/00A61P35/00A61P35/04
CPCA61P35/00A61P35/04C07J71/0005
Inventor 黄文李幼平余睽张俊华辛光钮海张伯礼
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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