Aromatic phenol quaternary ammonium salt antibacterial peptide mimetic with antibacterial activity and preparation method thereof

A technology of antibacterial activity and antimicrobial peptide, applied in the field of medicinal chemistry, can solve the problems of easy degradation, weak selectivity, and high production cost of natural antimicrobial peptides, and achieve excellent antibacterial activity, high selectivity, and solve the problem of drug-resistant bacteria.

Active Publication Date: 2020-11-03
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the high production cost of natural antimicrobial peptides, they cannot be mass-produced, are easily degraded in the body, and some antimicrobial peptides have high toxicity and weak selectivity.

Method used

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  • Aromatic phenol quaternary ammonium salt antibacterial peptide mimetic with antibacterial activity and preparation method thereof
  • Aromatic phenol quaternary ammonium salt antibacterial peptide mimetic with antibacterial activity and preparation method thereof
  • Aromatic phenol quaternary ammonium salt antibacterial peptide mimetic with antibacterial activity and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] The preparation of embodiment 1 compound 1a

[0062] In a round bottom flask (500 mL), weigh 1,4-bis(2-hydroxyethoxy)benzene (5 g, 25 mmol) and triphenylphosphine (15.7 g, 60 mmol) and dissolve in anhydrous acetonitrile (120 mL) , and then keeping the temperature at 0° C., carbon tetrabromide (19.9 g, 60 mmol) was slowly added to the above system. Then the temperature was raised to room temperature 25° C., and stirred for 4 hours under the protection of nitrogen. After the reaction, ice water (200mL) was added to the system, and the product was precipitated. The solid was obtained by filtration and washed with methanol / water (3:2, 3×100mL) for 3-4 times. The crude product was further purified by recrystallization in methanol to obtain pure product.

[0063] 1a: 1 H NMR (400MHz, CDCl 3 )δ6.86(s,4H),4.24(t,J=6.3Hz,4H),3.61(t,J=6.3Hz,4H). 13 C NMR (101MHz, CDCl 3 )δ152.85, 116.12, 68.74, 29.25.

Embodiment 2

[0064] The preparation of embodiment 2 compound 1b

[0065] In a round bottom flask (250mL), take hydroquinone (8g, 72.65mmol, 1eq) and dissolve it in acetone (150mL), then add dibromopropane (44g, 217.96mmol, 3eq) and potassium carbonate (45.18g, 326.94mmol, 4.5eq) stirred to dissolve the compound, added magneton, and heated to reflux for 24 hours under the protection of nitrogen. After the reaction was completed, the system was lowered to room temperature, filtered, and the filter residue was washed 3-4 times with dichloromethane. The filtrate was washed 3-4 times with water, then washed 3-4 times with saturated aqueous sodium chloride solution, and finally the solution was dried with anhydrous sodium sulfate, filtered, evaporated to dryness with a rotary evaporator, and separated by a silica gel column (petroleum ether: ethyl acetate Ester = 30:1) to give a white solid.

[0066] 1b: 1 H NMR (400MHz, CDCl 3 )δ6.84(s,4H),4.05(t,J=5.8Hz,4H),3.60(t,J=6.5Hz,4H),2.33–2.25(m,4...

Embodiment 3

[0067] Preparation of Compound 1c in Example 3: The dibromoalkane used was dibromobutane, which was separated on a silica gel column (petroleum ether: ethyl acetate = 30:1). The preparation method was the same as in Example 2.

[0068] 1c: 1 H NMR (400MHz, CDCl 3 )δ6.81(s,4H),3.93(t,J=6.1Hz,4H),3.48(t,J=6.7Hz,4H),2.11–2.00(m,4H),1.96–1.83(m,4H ). 13 C NMR (101MHz, CDCl 3 )δ153.11, 115.44, 77.41, 77.09, 76.77, 67.49, 33.55, 29.54, 28.03.

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Abstract

The invention belongs to the technical field of medicine chemistry, and discloses an aromatic phenol antibacterial peptide simulant with anti-drug resistance activity and no obvious toxicity and a preparation method thereof. The target product is obtained through a reaction of 3 to 4 steps, and the main structure is shown below. Vitro antibacterial activity experiment proves that most of the compounds have good activity on gram-positive bacteria staphylococcus aureus and enterococcus faecalis, gram-negative bacteria large intestine angstrom bacillus and notrophomonas maltophilia, and shows that the compounds have excellent broad-spectrum antibacterial activity; meanwhile, the extracorporeal red blood cell hemolytic data shows that the toxicity is small, and the method has good selectivity.Part of the compounds shows excellent antibacterial activity in superbacteria including methicillin-resistant staphylococcus aureus (MRSA), NDM-1 and KPC-2 enzyme. Therefore, the compounds are expected to be used as a new antibacterial candidate drug.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and discloses an aromatic phenol quaternary ammonium salt antibacterial peptide mimic with anti-drug-resistant bacteria activity and no obvious toxicity and a preparation method thereof. Background technique [0002] The discovery and widespread use of antibiotics has indelible significance in the development of human civilization. According to different mechanisms, they are divided into aminoglycosides, tetracyclines, chloramphenicols, macrolides, lincomycetes, which affect bacterial protein synthesis. β-lactams that interfere with bacterial cell wall synthesis; polymyxins that damage bacterial cell membranes; sulfonamides and trimethoprim that interfere with folic acid metabolism; quinolones that affect nucleic acid metabolism, etc. However, due to the non-standard use of antibiotics, severe bacterial resistance problems have emerged, and even cross-resistance and multi-drug resista...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C217/18C07C217/16C07C213/02A61P31/04
CPCA61P31/04C07C217/16C07C217/18Y02A50/30
Inventor 张恩楚文超杨燚秦上尚杨倩王亚娜崔得运化永刚白鹏燕
Owner ZHENGZHOU UNIV
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