Saucernetin structure simplifier and preparation method, medicinal composition and application thereof

A compound and halogen technology, applied in the field of medicine, can solve the problems of limited sources, complex structure of natural products, difficult preparation, etc., and achieve excellent effects.

Active Publication Date: 2012-11-28
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

And it also has strong inhibitory activity to various hypoxia-induced CDKN1A, VEGF and GLUT-1 genes (J.Nat.Prod., 2004,67,767-771; Biochem.Biophy.Res.Commun., 2005,333 , 1026-1033.), but this type is difficult to extract and separate, so the sources are limited
In addition, the structure of natural products is complex, and it is difficult to prepare by synthetic methods.

Method used

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  • Saucernetin structure simplifier and preparation method, medicinal composition and application thereof
  • Saucernetin structure simplifier and preparation method, medicinal composition and application thereof
  • Saucernetin structure simplifier and preparation method, medicinal composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Step A: Add o-methoxyphenol 10g (80.56mmol), sodium hydroxide 5.76g (144mmol), methanol 100mL in a 250mL round bottom flask, add elemental iodine 20.4g (80.3mmol) at -4°C, and at this temperature After reacting for 1h, TLC showed that it was complete, stop the reaction, pour into water, extract with ethyl acetate, wash with sodium dithionite, wash with saturated sodium chloride, dry over anhydrous sodium sulfate, filter, evaporate the solvent, and obtain 10.6 g of the crude product on a silica gel short column. rate 53%

[0082]

[0083] 1 H NMR (300M, CDCl 3 , δppm) 7.18 (d, 1H, J=8.4Hz, Ar-H), 6.86 (s, 1H, Ar-H), 6.69 (d, 1H, J=

[0084] 8.1Hz, Ar-H), 5.57(s, 1H, OH) 3.88(s, 1H, -OCH 3 )

[0085] Step B: Add compound 110.6g (42.4mmol) to a 200mL round bottom flask, dissolve in 50mL of anhydrous DMF, add anhydrous potassium carbonate 22g (159mmol), slowly add 1.39mL (42.4mmol) of benzyl bromide in an ice bath, rt After 2 hours of reaction, TLC showed that the r...

experiment example 1

[0153] Experimental example 1. Inhibitory effect of triasprosin-8 and its derivatives on HIF-1 activity

[0154] (1) Method

[0155] Report gene assay

[0156] The T47D cell model transiently co-transfected with pGL2-TK-3HRE / pRL-CMV plasmid was used for detection. pGL2-TK-3HRE is a firefly luciferase plasmid containing HRE (HIF-1 binding response element), and pRL-CMV is a Renilla luciferase plasmid. Under hypoxic conditions, pGL2-TK-3HRE highly expressed firefly luciferase in cells, but pRL-CMV was not affected.

[0157] 1. Human breast cancer cells T47D (ATCC) use RPMI-1640 containing 10% FBS, penicillin (100IU / ml), streptomycin (100g / ml) in normal oxygen 21% O 2 , 5%CO 2 cultured under conditions. T47D cells were seeded in 96-well plate, 45000 cells / well, 21% O 2 , 5%CO 2After 48 hours of culture, the fusion degree is about 90-95%. Apply lipofectamine 2000 for transient co-transfection, add 0.5 μl lipo2000 to each well, pGL2-TK-3HRE, pRL-CMV respectively 0.2 μg, 0.01...

experiment example 2、 3

[0172] Experimental Example 2. Inhibitory Effect of Triasprosin-8 and Its Derivatives on Tumor Cell Growth under Normal Oxygen Conditions

[0173] (1) Method

[0174] Determination of Inhibitory Effects of Triasprosin and Its Derivatives on Tumor Cell Growth by MTT Method

[0175] Digest the cells in the logarithmic growth phase with 0.25% trypsin-EDTA, prepare a single-cell suspension with a certain concentration, and inoculate 100-2000 cells / well in a 96-well plate according to the difference in cell growth rate, each well Add 100 μL of cell suspension. After 24 hours, add fresh medium containing different concentrations of compounds and corresponding solvent controls, add 100 μL to each well (DMSO final concentration 50 .

[0176] Inhibition rate (%)=(average OD value of the control group-average OD value of the administration group) / average OD value of the control group×100%

[0177] (2) Results

[0178] Table 4. Inhibitory effect of triasprosin-8 on tumor cell growth ...

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PUM

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Abstract

The invention discloses a saucernetin structure simplifier and a preparation method, a medicinal composition and application thereof, and in particular relates to a compound shown as a general formula I or an isomer and salt thereof, and a preparation method for the compound. A new medicinal composition comprises an effective dose of compound shown as the formula I and a pharmacodynamically acceptable carrier. The invention also discloses application of the compound to preparation of medicines for preventing and / or treating tumors such as neuroglioblastoma, melanoma, gastric cancer, lung cancer, breast cancer, kidney cancer, liver cancer, oral epidermal carcinoma, cervical cancer, ovarian cancer, pancreatic cancer, prostatic cancer, colon cancer and rectum adenocarcinoma.

Description

technical field [0001] The invention relates to a novel triasprosin structural simplification, a preparation method thereof, a pharmaceutical composition containing them, and its use as a medicine, especially as an antitumor medicine, belonging to the technical field of medicine. Background technique [0002] At present, it is believed that due to the structural and functional abnormalities of the blood vessels of most solid tumors, they cannot meet the needs of nutrients and oxygen for the rapid growth of tumor cells, resulting in a special hypoxic and acidic microenvironment for solid tumors, which in turn promotes the cancer cells to respond to cancer cells. Hypoxia produces an adaptive response. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that plays a regulatory role in a series of responses triggered by changes in intracellular oxygen content. It is an important factor for the survival of cancer cells under ischemic conditions. Immunohistochemical stu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C43/23C07C49/84C07C41/26C07D317/54A61K31/09A61K31/12A61K31/36A61P35/00
CPCC07C49/84C07D317/54A61K31/12C07C2101/08C07C43/23A61K31/36A61P35/00C07C2601/08
Inventor 谢平陈晓光焦晓臻刘晓宇李燕张翼郎立伟王丽萍李人则
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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