Asymmetric curcumin compounds and their application in the preparation of anti-gastric cancer drugs

A technology of curcumin and compounds, applied in the direction of active ingredients of heterocyclic compounds, drug combinations, antineoplastic drugs, etc.

Active Publication Date: 2020-09-25
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are few reports on curcumin analogs with asymmetric structures, and there are very few reports on curcumin analogs based on asymmetric structures that target the NF-κB pathway to exert anti-tumor activity.

Method used

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  • Asymmetric curcumin compounds and their application in the preparation of anti-gastric cancer drugs
  • Asymmetric curcumin compounds and their application in the preparation of anti-gastric cancer drugs
  • Asymmetric curcumin compounds and their application in the preparation of anti-gastric cancer drugs

Examples

Experimental program
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Effect test

Embodiment 1

[0028] The synthesis of embodiment 1 compound

[0029] Weigh 50mmoL of pyrone and 75mmoL of morpholine into a round bottom flask, add 50mL of reaction solvent cyclohexane and 1g of catalyst p-toluenesulfonic acid. After reflux at 90° C. for 4 h, the reaction solvent was removed by rotary evaporation to obtain a small amount of light yellow liquid. Add 25mmoL of 3-methoxy-4-hydroxybenzaldehyde to the above-mentioned round-bottomed flask containing light yellow liquid, add 30mL of absolute ethanol as a reaction solvent, and reflux at 78°C. Detected by TLC, the end point of the reaction was the appearance of a symmetrical by-product that was yellow at 365 nm. After the above reaction solution is cooled, add an appropriate amount of dilute hydrochloric acid to adjust the pH to 2-3, stir at room temperature to produce a precipitate, filter, and dry to obtain a crude intermediate product for later use.

[0030] Weigh each 1mmoL of the above-mentioned intermediate crude product and...

Embodiment 2

[0044] Example 2 Screening of S series compounds for growth inhibition of gastric cancer cells.

[0045] The inhibitory effect of curcumin analogues on the growth of gastric cancer cells was detected by MTT assay. The results of these analogs on gastric cancer cells BGC-823, SGC-7901 and MFC were as follows figure 2 A, B and C are shown. The inhibition rate of most of the compounds on the growth of three gastric cancer cell lines reached more than 60%. The inhibitory activity of compounds S01, S02, S04, S06, S07 and S12-14 on the proliferation of BGC-823 cells is higher than that of BMS-345541, and more than ten times that of curcumin. The inhibitory activity of compounds S01-07 and S12-14 on the proliferation of SGC-7901 cells was higher than that of BMS-345541, and more than twice that of curcumin. The inhibitory activity of compounds S04, S06, S07 and S12 on MFC cell proliferation was higher than that of BMS-345541 and more than twice that of curcumin. The four compoun...

Embodiment 3

[0046] Example 3 Effect of compound S06 on the growth of gastric cancer cells.

[0047] The compound S06 with better activity was screened from the MTT experiment, and further biological evaluation was carried out. The IC of compound S06 on BGC-823 and SGC-7901 cell lines was measured 50 . The results showed that the IC of S06 on BGC-823 cells 50 IC of 3.51μM on SGC-7901 cells 50 1.55μM ( image 3 A). The effect of compounds on cell proliferation was studied by colony formation assay. Gastric cancer cells were treated with different concentrations of S06 (1, 2.5, 5 μM). The results showed that S06 could dose-dependently inhibit the formation of cell colonies ( image 3 B). There was almost no visible colony formation in the group treated with S06 at a concentration of 5 μM. The curative effect of S06 at 5μM was significantly better than that of the positive drug BAY11-7082 at the same concentration. It can be seen that compound S06 has medicinal prospects.

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Abstract

The invention belongs to the field of medicinal chemistry and particularly relates to an application of asymmetric curcumine compounds to preparation of anti-gastric-cancer drugs. The compounds can effectively inhibit growth of gastric cancer cells BGC-823, SGC-7901 and MFC, inhibit formation of gastric cancer cell colonies, inhibit NF-kappaB signaling pathways in the gastric cancer cells, down-regulate expression of anti-apoptotic protein Bcl-2, up-regulate expression of apoptin Bax and induce gastric cancer cell apoptosis, wherein the active compound S06 can effectively enhance anti-gastric-cancer activity of irinotecan and can serve as a potential anti-gastric-cancer drug.

Description

technical field [0001] The present invention belongs to the field of medicinal chemistry. Specifically, the present invention relates to the application of specific asymmetric curcuminoid compounds in anti-gastric cancer. These asymmetric curcuminoid compounds inhibit NF-κB to achieve good anti-gastric cancer and Sensitization of irinotecan against gastric cancer. Background technique [0002] Gastric cancer is one of the malignant tumors with the highest incidence rate in the world, and its death rate ranks second among all kinds of cancers. Surgery is a radical method for early gastric cancer. However, most patients are diagnosed at an advanced stage when they are diagnosed with cancer and lose the opportunity for surgery. Even after radical resection for early gastric cancer patients, the postoperative recurrence rate and metastasis rate are high. Therefore, chemotherapy still plays an important role in the treatment of gastric cancer. At present, the first-line chemoth...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D309/38C07D407/06A61K31/351A61K31/36A61P35/00
CPCA61K31/351A61K31/36C07D309/38C07D407/06
Inventor 吴建章李物兰张珊珊仇佩虹徐清梁广
Owner WENZHOU MEDICAL UNIV
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