阅读说明：本技术 Germacradienol及其衍生物用于制备治疗神经母细胞瘤的药物的用途 (Application of Germacradienol and derivatives thereof in preparing medicine for treating neuroblastoma ) 是由 梁淑红 赵杰 李砺锋 沈志博 薛文华 于 2019-10-12 设计创作，主要内容包括：本发明公开了Germacradienol及其衍生物用于制备治疗神经母细胞瘤的药物的用途。本发明的试验结果表明,化合物Germacradienol及其衍生物9β-hydroxyl germacradienol和2-oxygermacradienol对神经母细胞瘤具有显著增殖抑制作用,IC50值均达到nM级别,且9β-hydroxyl germacradienol的增殖抑制活性最强,为Germacradienol的50倍以上,另外2-oxygermacradienol的增殖抑制活性也达到Germacradienol的20倍以上,三者均具有开发成治疗神经母细胞瘤的药物的前景。(The invention discloses application of Germacradienol and derivatives thereof in preparing a medicine for treating neuroblastoma. The test result of the invention shows that the compounds Germacrodienol and the derivatives 9 beta-hydroxy germacrantinol and 2-oxygermacrantinol have obvious proliferation inhibition effect on neuroblastoma, the IC50 value reaches nM level, the proliferation inhibition activity of the 9 beta-hydroxy germacrantinol is strongest and is more than 50 times of Germacrodienol, in addition, the proliferation inhibition activity of the 2-oxygermacrantinol also reaches more than 20 times of Germacrodienol, and the three have the prospect of developing the medicine for treating neuroblastoma.)

1. Use of a compound of the following chemical structure for the preparation of a medicament for the treatment of neuroblastoma:

wherein R is₁is-H or-OH, R₂is-H or ═ O.

2. Use according to claim 1, characterized in that the compound is one of the following compounds:

3. a medicament for treating neuroblastoma, characterized in that the active ingredient is a compound of the following chemical structure:

wherein R is₁is-H or-OH, R₂is-H or ═ O.

4. The medicament of claim 3, wherein the compound is one of the following compounds:

5. the medicament according to claim 3 or 4, characterized in that: also contains pharmaceutically acceptable auxiliary materials, and is prepared into pharmaceutically acceptable dosage forms.

6. The medicament of claim 5, wherein: the auxiliary materials comprise liquid, solid or semisolid auxiliary materials.

7. The medicament of claim 5, wherein: the dosage forms comprise tablets, capsules and injections.

Technical Field

The invention belongs to the field of medicines, relates to development of antitumor medicines, and particularly relates to application of Germacradienol and derivatives thereof in preparation of medicines for treating neuroblastoma.

Background

Neuroblastoma is a solid tumor with the highest pediatric mortality, has high malignancy, poor prognosis, strong heterogeneity and large difference in the effects of radiotherapy and chemotherapy, and some patients are insensitive to radiotherapy and chemotherapy and have rapid disease deterioration. The application of chemotherapy drugs is an indispensable means for prolonging the survival time of patients, and the development of new drugs with good curative effect and few adverse reactions is hoped for the life continuation of patients (elemene has inhibition effect on neuroblastoma proliferation, volume 46, phase 12, 2017, university of Chinese medical science, journal).

Zhongjing julian and the like found that elemene extracted from natural curcuma wenyujin of Zingiberaceae has an inhibition effect on the proliferation of neuroblastoma, is time-dependent and concentration-dependent, and has a prospect of being developed into an anti-neuroblastoma medicament (the inhibition effect of elemene on the proliferation of neuroblastoma, volume 46, 12 th period, 2017, of Chinese medical university).

Zhang Haili et al found that resveratrol can inhibit the proliferation of human neuroblastoma cells to play a role in resisting cancer, and shows dual dependence of concentration and time. The effect of the resveratrol on inhibiting the proliferation of human neuroblastoma cells is more obvious as the action time of the resveratrol is increased within a certain concentration range, and the effect of the resveratrol on inhibiting the proliferation of cells is also in an upward trend when the concentration of the resveratrol is increased within a certain time range (research on the effect of the resveratrol on the proliferation of SH-SY5Y human neuroblastoma cells, volume 40, 3, 6 months 2017, Ministry of Binzhou medical college).

The discovery of xiabao good and the like shows that the ginsenoside Rh2 has an in-vitro inhibition effect on neuroblastoma, and realizes a process of inhibiting migration and invasion of neuroblastoma by up-regulating a pro-apoptotic protein Bax, down-regulating an anti-apoptotic protein Bcl-2 and a matrix metalloproteinase MMP-2 (the influence of ginsenoside Rh2 on the proliferation, apoptosis, migration and invasion of the neuroblastoma SH-SY5Y, and the modern tumor medicine 2019).

Germacradienol is also a natural product, and 9 beta-hydroxy germacriadienol and 2-oxygermacriadienol are two derivatives thereof, and the chemical structures of the derivatives are shown in the specification.

Disclosure of Invention

The invention aims to provide application of Germacradienol and derivatives thereof in preparing a medicine for treating neuroblastoma.

The above purpose of the invention is realized by the following technical scheme:

use of a compound of the following chemical structure for the preparation of a medicament for the treatment of neuroblastoma:

wherein R is₁is-H or-OH, R₂is-H or ═ O.

Further, the compound is one of the following compounds:

a medicine for treating neuroblastoma comprises the following active ingredients:

wherein R is₁is-H or-OH, R₂is-H or ═ O.

Further, the compound is one of the following compounds:

further, the composition also contains pharmaceutically acceptable auxiliary materials and is prepared into pharmaceutically acceptable dosage forms.

Still further, the adjuvant comprises a liquid, solid, or semi-solid adjuvant.

Still further, the dosage forms include tablets, capsules, injections.

Has the advantages that:

the test result of the invention shows that the compounds Germacrodienol and the derivatives 9 beta-hydroxy germacrantinol and 2-oxygermacrantinol have obvious proliferation inhibition effect on neuroblastoma, the IC50 value reaches nM level, the proliferation inhibition activity of the 9 beta-hydroxy germacrantinol is strongest and is more than 50 times of Germacrodienol, in addition, the proliferation inhibition activity of the 2-oxygermacrantinol also reaches more than 20 times of Germacrodienol, and the three have the prospect of developing the medicine for treating neuroblastoma.

Detailed Description

The following examples are given to illustrate the essence of the present invention, but not to limit the scope of the present invention.