阅读说明：本技术 一种单端孢霉烯型化合物及其作用 (Trichothecene compound and application thereof ) 是由 李天笑 贾学伟 许春平 王颖 张宗欣 孟丹丹 刘彬 姚延超 于 2019-09-03 设计创作，主要内容包括：本发明提出了一种单端孢霉烯型化合物露湿漆斑醇,化合物的结构式为<Image he="154" wi="166" file="DEST_PATH_IMAGE002.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>,单端孢霉烯型化合物露湿漆斑醇对人胃癌细胞株MGC803的半数抑制浓度为5.4±0.5μM；对人肺腺癌细胞细胞株NCI-H1975的半数抑制浓度为28.7±1.3μM,可在制备治疗胃癌和肺癌药物前体中应用,为下一步的胃癌和肺癌药物的药效研究奠定了物质基础。(The invention provides a trichothecene compound wet-spot pain alcohol, and the structural formula of the compound is The median inhibitory concentration of the trichothecene compound of the rhodanese wet spot alcohol to human gastric cancer cell strain MGC803 is 5.4 +/-0.5 mu M; the half inhibition concentration of human lung adenocarcinoma cell line NCI-H1975 is 28.7 +/-1.3 mu M, and the derivative can be applied to preparation of precursors of medicaments for treating gastric cancer and lung cancer, and lays a material foundation for the next pharmacodynamic study of gastric cancer and lung cancer medicaments.)

1. The trichothecene compound wet-exposed urushiol is characterized in that the structural formula of the compound is shown in the specification

2. The use of a trichothecene-type compound vinca-sumac alcohol according to claim 1 in the preparation of a prodrug for the treatment of gastric cancer and lung cancer.

3. A process for the preparation of the trichothecene-type compound sumac alcohol of claim 1, comprising the steps of:

(1) activating the myrothecium roridum to form a seed solution, and culturing and fermenting in a solid culture medium;

(2) carrying out cold leaching extraction on the fermentation product obtained in the step (1), and then carrying out reduced pressure concentration to obtain a crude extract;

(3) and (3) eluting the crude extract in the step (2) by using macroporous resin column chromatography, and then separating and purifying the target sub-component by using high performance liquid chromatography.

4. The method according to claim 3, wherein the preparation of the trichothecene-type compound lucernol according to claim 1 is carried out by soaking 60 ~ 100g rice in 90 ~ 150mL water overnight, and autoclaving at 105 ~ 115 ℃ for 20 ~ 40 min.

5. The method for preparing the trichothecene-type compound sumac alcohol of claim 1 according to claim 3, wherein the gradient of elution by macroporous resin column chromatography in step (3) is 10% ~ 100% methanol-water 100%.

6. The method for preparing the trichothecene-type compound wet sumac alcohol of claim 1, according to claim 3, wherein the target subgroup in step (3) is 20% ~ 40% methanol-water segment.

7. The process for preparing the trichothecene-type compound neratide according to claim 3, wherein the eluent obtained by the high performance liquid chromatography in step (3) is methanol-water with a methanol-water volume ratio of 30% ~ 40%.

Technical Field

The invention belongs to the technical field of natural medicines, and particularly relates to a trichothecene compound and an effect thereof.

Background

Trichothecenes are toxins produced by fungi of the genera trichothecene (trichothecium sp.), Myrothecium (myrothecium sp.), Fusarium (fusarium sp.), Trichoderma (trichodermatum sp.), and the like. The reported trichothecene compounds have various biological activities, and the antitumor activity of the trichothecene compounds is outstanding, so that the trichothecene compounds are hot spots of current research. Research shows that the trichothecenes cyclized at 10 and 13 positions, such as the humicola fusca, have low toxicity, good safety, no reduction of the anti-tumor effect and better pharmaceutical prospect than the non-cyclized compound. At present, no activity test report of the compounds on human gastric cancer MGC803 and lung adenocarcinoma cell NCI-H1975 cell strains exists.

Therefore, the technical personnel in the field need to solve the problems of providing the trichothecene compounds cyclized at 10 and 13 positions, researching the antitumor effect of the compounds and laying a material foundation for clinical application.

Disclosure of Invention

The invention is based on at least one of the technical problems, provides a trichothecene new compound with an anti-tumor effect and a preparation method thereof, and the compound provides an effective prodrug for the development of anti-tumor drugs and lays a material foundation for the next pharmacodynamic study.

In view of the above, the invention provides a trichothecene compound-lukeshichun, the structural formula of which is

According to a second aspect of the present invention, there is provided the use of a trichothecene-type compound luculid for the preparation of a prodrug for the treatment of gastric and lung cancer.

According to a third aspect of the present invention, there is provided a process for the preparation of a trichothecene-type compound sumac alcohol, comprising the steps of:

(1) activating the myrothecium roridum to form a seed solution, and culturing and fermenting in a solid culture medium;

(2) carrying out cold leaching extraction on the fermentation product obtained in the step (1), and then carrying out reduced pressure concentration to obtain a crude extract;

(3) and (3) eluting the crude extract in the step (2) by using macroporous resin column chromatography, and separating and purifying the target sub-component by using high performance liquid chromatography.

Further, the preparation method of the solid culture medium comprises the following steps: 60-100 g of rice and 90-150 mL of water are soaked overnight and then sterilized for 20-40 min under high pressure at 105-115 ℃.

Further, the macroporous resin column chromatography elution gradient in the step (3) is 10-100% of methanol-water.

Further, the target subgroup in the step (3) is 20-40% methanol-water section.

Further, the eluent of the high performance liquid chromatography is methanol-water with the volume ratio of methanol to water of 30-40 percent.

The invention provides a trichothecene compound and an effect thereof, and the trichothecene compound has the following technical effects: the invention provides a novel 10, 13-site cyclized trichothecene compound liqid-spot alcohol, and the semiinhibitory concentration of the liqid-spot alcohol to human gastric cancer cell strain MGC803 is found to be 5.4 +/-0.5 mu M in subsequent research; the half inhibition concentration of human lung adenocarcinoma cell line NCI-H1975 is 28.7 +/-1.3 mu M, and the derivative can be applied to preparation of precursors of medicaments for treating gastric cancer and lung cancer, and lays a material foundation for the next pharmacodynamic study of gastric cancer and lung cancer medicaments.

Drawings

FIG. 1 shows key HMBC and HMBC of lacustrol wet-on-wet¹H-¹HCOSY signal.

FIG. 2 shows a high resolution mass spectrum of the wet sumac alcohol.

FIG. 3 shows the preparation of laccolin¹H-NMR chart.

FIG. 4 shows the preparation of laccolin¹³C-NMR chart.

FIG. 5 shows the presence of lacchol¹H-¹HCOSY diagram.

FIG. 6 shows HSQC plots of wet lacchol.

FIG. 7 shows an HMBC diagram of wet lacustrol.

FIG. 8 shows the ROESY plot of lacchol wet.

Detailed Description

In order that the above objects, features and advantages of the present invention can be more clearly understood, a more particular description of the invention will be rendered by reference to the appended drawings. It should be noted that the embodiments of the present invention and features of the embodiments may be combined with each other without conflict.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, however, the present invention may be practiced in other ways than those specifically described herein, and therefore the scope of the present invention is not limited by the specific embodiments disclosed below.