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Aromatic polyketide compounds talaromyoxaones A and B, preparation method and application thereof

A technology of compounds and medicinal salts, applied in biochemical equipment and methods, methods based on microorganisms, fungi, etc., can solve few problems

Active Publication Date: 2021-10-01
SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are few reports on PTPs inhibitors derived from marine fungi

Method used

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  • Aromatic polyketide compounds talaromyoxaones A and B, preparation method and application thereof
  • Aromatic polyketide compounds talaromyoxaones A and B, preparation method and application thereof
  • Aromatic polyketide compounds talaromyoxaones A and B, preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] (1) The fermentation medium is prepared by the following method: by mass fraction, add 1% glucose, 1% starch, 0.1% KH to tap water 2 PO4, 0.1% MgSO 4 ·7H 2 O, 0.1% peptone, 3% sea salt, and adjust the pH of the medium to 6.5 with NaOH or HCl aqueous solution. Configure 50L of fermentation medium, and then divide into 1L Erlenmeyer flasks, about 300 mL of medium per bottle. Prepared by autoclaving at 115°C for 25 minutes.

[0024] (2) Preparation of fermentation broth and mycelium: Inoculate the fungus T.purpureogenus SCSIO 41517 on a flat plate containing PDA medium. After the fungus grows spores, transfer the spores and mycelium from the flat plate to In the Erlenmeyer flask containing the fermentation medium, culture it on a shaker at 28°C for 2-3 days to make a seed liquid, and inoculate the seed liquid into the fermentation medium with a pipette gun (300mL of fermentation medium is contained in a 1L Erlenmeyer flask), The fermentation broth and mycelia were harv...

Embodiment 2

[0037] The protein tyrosine phosphatase activity test of embodiment 2 compound Talaromyoxaones A and B

[0038] The human protein tyrosine phosphatase CDC25B, SHP2, MEG2, SHP1, TCPTP, CD45 or PTP1B genes were cloned into Escherichia coli (Escherichia coli), then expressed and purified. Enzyme inhibitory activity was measured using p-nitrophenylphosphate (pNPP) as a substrate in 96-well plates containing 100 μL of reaction mixture per well. Human recombinant CDC25B, SHP2, MEG2, SHP1, TCPTP, CD45 or PTP1B (0.05 μg) were added to 50 μL of reaction buffer containing 50 mM HEPES, 100 mM NaCl, 1 mM EDTA and 1 mM dithiothreitol (DTT) (pH6.5), and then The compound samples to be tested (compounds 1-2) were added to each 96-well plate. Na 3 VO 4 As a positive control, DMSO as a negative control was used to evaluate this high-throughput screening system. After 15 min pre-incubation at room temperature, 50 μL of buffer containing 50 mM pNPP was added and incubation was continued at 3...

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Abstract

The invention discloses two aromatic polyketide compounds Talaromyoxaones A and B, their preparation method and their application in the preparation of protein tyrosine phosphatase SHP1 inhibitors, SHP2 inhibitors, MEG2 inhibitors and CD45 inhibitors. The structure of the aromatic polyketone compound is shown in formula (I). Talaromyoxaones A and B are isolated from the fermentation extract of Talaromyces purpureogenus SCSIO 41517. It has been proved by experiments that the aromatic polyketide Talaromyoxaones A and B of the present invention have the activity of inhibiting protein tyrosine phosphatases SHP1, SHP2, MEG2 and CD45 , they can be used in the study of these four enzyme inhibitor lead compounds.

Description

technical field [0001] The invention belongs to the field of marine biology, and specifically relates to compounds Talaromyoxaones A and B, a preparation method thereof, and an application in the preparation of protein tyrosine phosphatase MEG2 inhibitors, SHP1 inhibitors, SHP2 inhibitors or CD45 inhibitors. Background technique [0002] The abnormal expression level and activity of protein tyrosine phosphatase (PTP) in the human body will lead to major human diseases such as diabetes and cancer, and it has great application potential to control diseases and screen and discover PTP inhibitors by mediating at the PTP level. Abnormal activity of PTPs can lead to disordered regulation of tyrosine phosphorylation, which is an important factor in many human diseases including diabetes, rheumatoid arthritis, myasthenia gravis, lupus erythematosus and cancer, vascular diseases, neurological and metabolic diseases, etc. reason. For example, SHP2 mutations in germline or somatic cel...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D493/10C12P17/18C12N1/14A61P3/10A61P35/00A61P35/02A61P19/02A61P21/04A61P3/00A61P25/00C12R1/645
CPCA61P3/00A61P3/10A61P19/02A61P21/04A61P25/00A61P35/00A61P35/02C07D493/10C12N1/14C12P17/181
Inventor 漆淑华梁潇
Owner SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI