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Anthraquinone compound, its preparation method and application in preparation of enzyme inhibitor

A compound and inhibitor technology, applied in the field of marine biology, can solve problems such as easy induction of drug resistance and large adverse reactions

Active Publication Date: 2020-04-10
SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0002] At present, the diagnosis and treatment of malignant tumors is still one of the biggest challenges in the medical field. Although traditional malignant tumor treatment methods such as chemotherapy and radiotherapy have been continuously developed, they still have certain limitations and disadvantages, such as large adverse reactions and easy induction Drug resistance, etc.

Method used

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  • Anthraquinone compound, its preparation method and application in preparation of enzyme inhibitor
  • Anthraquinone compound, its preparation method and application in preparation of enzyme inhibitor
  • Anthraquinone compound, its preparation method and application in preparation of enzyme inhibitor

Examples

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Embodiment 1

[0032] (1) Preparation of fermentation medium: 10g of glucose, 20g of mannitol, 20g of maltose, 0.5g of corn starch, 10g of monosodium glutamate, KH 2 PO 4 0.5g, 3g of yeast extract, and 30g of sea salt were mixed, the volume was adjusted to 1L with water, and the pH was adjusted to 6.5 to obtain 1L of medium, and the medium was configured in this way. The culture medium was put into about 200 1000-mL Erlenmeyer flasks, each of about 300 mL, and autoclaved at 115° C. for 25 minutes.

[0033](2) Preparation of fermentation broth: The fungus A.tenuissma JX156349 was grown in a plate medium suitable for fungi, and after the fungi grew spores, the fungi were moved from the plate to a triangular flask filled with water with a bamboo stick, and the The fungus was inoculated into the fermentation medium by a liquid gun (300 mL of fermentation medium was contained in a 1L conical flask), and the fermentation broth was collected after standing at room temperature (26° C.) for 30 days...

Embodiment 2

[0050] Phosphokinase and IDO1 Enzyme Inhibitory Activity Test of the Compounds of Example 2

[0051] (1) Phosphokinase inhibitory activity assay: Human phosphokinases PTP1B, SHP1, SHP2, MEG2 or TCPTP were cloned into Escherichia coli and purified. Enzyme inhibitory activity was assayed in 96-well plates using p-nitrophenyl phosphate (pNPP) as substrate with 100 μL of reaction mixture per well. Human recombinant PTP1B, SHP1, SHP2, MEG2orTCPTP (0.05 μg) was added to 50 μL of reaction buffer (pH 6.5) containing 50 mM HEPES, 100 mM NaCl, 1 mM EDTA, and 1 mM dithiothreitol (DTT), and each 96-well plate was separated Add samples of compounds to be tested (compounds Anthrininone A, Anthrininone B, Anthrininone C and 6-O-methylalaternin). Na 3 VO 4 As a positive control, DMSO was used as a negative control to evaluate this high-throughput screening system. After a 15 min pre-incubation at room temperature, 50 μL of buffer containing 50 mM pNPP was added and the incubation was cont...

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Abstract

The invention discloses two novel anthraquinone compounds, namely Anthrininones B and C, as well as a preparation method and application thereof in preparing protein-tyrosine-phosphatase (PTPs) and indole-amine 2,3-dioxygenase 1 (IDO1) inhibitors, and further discloses application of 6-O-methylalaternin in preparing the PTPs and the IDO1 inhibitors, and application of Anthrininone A in preparing the IDO1 inhibitors. The compounds Anthrininones B and C have structural formulae (I) shown in the specification. The compounds Anthrininones B and C and 6-O-methylalaternin are separated from a fermentation liquid of Alternaria tenuissma JX156349, and can be applied to study on lead compounds of PTP inhibitors and DIO1 inhibitors.

Description

technical field [0001] The invention belongs to the field of marine biology, and in particular relates to four anthraquinone compounds and their preparation method and application in the preparation of enzyme inhibitors, in particular to the preparation of protein tyrosine phosphatase or indoleamine-2,3-diaddition Application of Oxygenase 1 Inhibitors. Background technique [0002] At present, the diagnosis and treatment of malignant tumors is still one of the biggest challenges in the medical field. Although traditional malignant tumor treatment methods such as chemotherapy and radiotherapy have been continuously developed, they still have certain limitations and disadvantages, such as large adverse reactions and easy induction. resistance, etc. In recent years, with the deepening of tumor immunity-related research, immunotherapy has become a new hope for improving the prognosis of patients with malignant tumors. As one of many tumor immune cycle regulators, indoleamine 2...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D207/28C07C50/16A61K31/40A61K31/122A61K31/35A61P35/00C12P17/10C12P7/26C12R1/645
Inventor 漆淑华
Owner SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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