Cyclic hexadepsipeptide compound desotamide A4 and application thereof in preparation of antibacterial drugs

A technology of antibacterial drugs and compounds, applied in the field of natural products, to achieve the effect of enhanced activity

Active Publication Date: 2021-07-23
SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since the beginning of this century, the number of discoveries of new antibiotics has dropped sharply, while major drug-resistant pathogens have rapidly emerged and spread, which has caused many deaths. According to the 2016 "Global Antimicrobial Resistance Review" report, currently at least 700,000 people died of drug-resistant diseases, and it is estimated that by 2050, drug-resistant bacteria will kill 10 million people every year. Antibiotic resistance has brought global challenges to the safe and healthy development of public health. Research and development New antibiotics are imminent

Method used

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  • Cyclic hexadepsipeptide compound desotamide A4 and application thereof in preparation of antibacterial drugs
  • Cyclic hexadepsipeptide compound desotamide A4 and application thereof in preparation of antibacterial drugs
  • Cyclic hexadepsipeptide compound desotamide A4 and application thereof in preparation of antibacterial drugs

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Experimental program
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Effect test

Embodiment 1

[0016] Example 1: Solid-phase chemical synthesis and structural confirmation of desotamide A4

[0017] Prepare desotamide A4 by solid-phase chemical synthesis method by Shanghai Ziyu Biotechnology Co., Ltd., the specific steps are as follows ( figure 1 ):

[0018] (1) Connecting to the first amino acid: Add 2-Cl-Trt resin to a dry and clean peptide reaction column, swell with N,N-dimethylformamide (DMF) for 0.5 hours, wash and then drain. Add the first amino acid raw material Fomc-L-Asn, O-benzotriazole-tetramethyluronium hexafluorophosphate (HBTU), N,N-diisopropylethylamine (DIEA), DMF as a solvent, React for 1.5 hours.

[0019] (2) Blocking: Add methanol directly after the reaction, so that the resin does not agglomerate, and react for 30 minutes. Wash with dichloromethane (DCM) and DMF (15 mL each for 3 times, 1 minute each), and drain.

[0020] (3) Removal: add 10 mL of DMF solution containing 20% ​​(volume fraction) piperidine, blow with nitrogen for 15 minutes, remov...

Embodiment 2

[0031] Embodiment 2: Antibacterial activity test analysis of compound desotamides A4 to series of Gram-positive pathogenic bacteria

[0032] The inhibitory activity of the compound desotamides A4 against a series of Staphylococcus aureus was tested by microwell method. A series of Staphylococcus aureus was cultured in Mueller-Hinton (MH) broth medium. And prepare the sample solution before the experimental bacteria grow well. Concentrations of samples and positive controls were configured, and ampicillin and vancomycin were selected as positive controls. All samples were configured at 3200 μg / mL and dissolved in DMSO. Add 92 μL of sterile MH broth to the first column of the 96-well plate with a row gun, and add 50 μL of MH broth to the remaining columns, mark and cover for later use. Pipette 8 μL (the initial concentration is 128 μg / mL; if the initial concentration is 64 μg / mL, take 4 μL; if the initial concentration is 32 μg / mL, take 2 μL) and add the prepared sample or po...

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Abstract

The invention discloses a cyclic hexapeptide compound desotamide A4 and an application thereof in preparation of antibacterial drugs. The structural formula of the compound desotamide A4 is as shown in formula (I) . The cyclic hexapeptide desotamide A4 disclosed by the invention has a broad-spectrum anti-gram pathogenic bacterium effect. The test result shows that the desotamide A4 has good inhibitory activity (MIC is 8-32 [mu] g/mL) on a plurality of clinical drug-resistant staphylococcus aureus, enterococcus faecalis, micrococcus luteus, bacillus subtilis, simulated staphylococcus and staphylococcus haemolyticus including methicillin-resistant staphylococcus aureus; compared with an unmodified parent natural cyclic peptide compound desotamide A, the activity of the cyclic hexapeptide desotamide A4 disclosed by the invention is enhanced by 2-4 times, and the cyclic hexapeptide desotamide A4 has an important value in research and development of antibacterial drugs.

Description

Technical field: [0001] The invention belongs to the field of natural products, and in particular relates to a cyclic hexapeptide compound desotamide A4 and its application in the preparation of antibacterial drugs. Background technique: [0002] Infectious diseases have always been the "Second Enemy" that threatens human health, and antibiotics are the most effective means to treat infectious diseases. However, since the beginning of this century, the number of discoveries of new antibiotics has dropped sharply, while major drug-resistant pathogens have rapidly emerged and spread, which has caused many deaths. According to the 2016 "Global Antimicrobial Resistance Review" report, currently at least 700,000 people died of drug-resistant diseases, and it is estimated that by 2050, drug-resistant bacteria will kill 10 million people every year. Antibiotic resistance has brought global challenges to the safe and healthy development of public health. Research and development Ne...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/64A61K38/12A61P31/04
CPCC07K7/64A61P31/04A61K38/00Y02A50/30
Inventor 李青连许润宋永相李骏鞠建华
Owner SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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