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CN-121990932-A - Cationic compound with long-acting high antibacterial activity and preparation method thereof

CN121990932ACN 121990932 ACN121990932 ACN 121990932ACN-121990932-A

Abstract

The application discloses a cationic compound with long-acting high antibacterial activity and a preparation method thereof, wherein the molecular formula of the cationic compound is shown as formula 1. The cationic compound can damage the integrity of cell membranes of bacteria, so that the bacteria die, and particularly has good antibacterial activity on escherichia coli, staphylococcus aureus and methicillin-resistant staphylococcus aureus.

Inventors

  • ZHANG CANYANG
  • ZHAO LIANG
  • LI DAN
  • ZHANG XIAOPENG

Assignees

  • 清华大学深圳国际研究生院

Dates

Publication Date
20260508
Application Date
20241107

Claims (12)

  1. 1. A cationic compound comprising a 3, 5-dimethoxyphenoxy group and two quaternary ammonium groups in its molecular structure.
  2. 2. The cationic compound of claim 1, having the formula of formula 1, Wherein n is an integer from 2 to 20, m is an integer from 2 to 12, R, R ', R ", R'", R "" are each independently H, any one of F, cl, br, I, NO 2 ,CF 3 ,OCH 3 ,CN,NH 2 ,COOH,(CH 2 ) x and an aromatic ring, wherein x is selected from integers of 1-20.
  3. 3. The cationic compound of claim 2, wherein n = 6, 8, 10, 12 or 16.
  4. 4. The cationic compound of claim 2, wherein m = 6.
  5. 5. The cationic compound of claim 2, wherein R is H.
  6. 6. The cationic compound of claim 2, wherein the cationic compound has a formula as shown in formula 2.
  7. 7. A process for the preparation of a cationic compound comprising the steps of: dissolving 2, 6-dimethoxy-4-hydroxybenzaldehyde in N, N-dimethylformamide, adding dibromoalkane and potassium carbonate, and purifying after reaction to obtain solid 4-bromoalkoxy-2, 6-dimethoxy benzaldehyde; Dropwise adding benzyl chloride into an acetone solution of tetramethyl alkyl diamine, and reacting to obtain benzyl- (dimethylamino) -dimethyl alkyl amine; Dissolving 4-bromoalkoxy-2, 6-dimethoxy benzaldehyde and benzyl- (dimethylamino) -dimethyl alkylamine in acetonitrile, and reacting to obtain the cationic compound; Preferably, the molar ratio of the 2, 6-dimethoxy-4-hydroxybenzaldehyde to dibromoalkane to the potassium carbonate is 1:2-100:1-10; Preferably, the molar ratio of the benzyl chloride to the tetramethyl alkyl diamine is 1:2-100; further preferably, the molar ratio of the 4-bromoalkoxy-2, 6-dimethoxybenzaldehyde to benzyl- (dimethylamino) -dimethylalkylamine is 0.9-1.2:1.
  8. 8. The preparation method according to claim 7, wherein the dibromoalkane has a molecular formula shown in formula 3, Wherein n is selected from integers from 2 to 20; preferably, the molecular formula of the tetramethyl alkyl diamine is shown as formula 4, Wherein m is selected from integers from 2 to 12; Preferably, the molecular formula of the benzyl chloride is shown as formula 5, Wherein R, R ', R', R "" are each independently H, F, cl, br, I, NO 2 ,CF 3 ,OCH 3 ,CN,NH 2 ,COOH,(CH 2 ) x and an aromatic ring, wherein x is selected from an integer of 1 to 20.
  9. 9. The use of a cationic compound according to any one of claims 1 to 6 or a cationic compound according to claim 7 or 8 for antimicrobial, preferably for antimicrobial agents.
  10. 10. Use according to claim 9, wherein the antibacterial agent is a long-acting antibacterial agent, preferably the antibacterial agent is an inactivated or inhibited bacteria and fungi.
  11. 11. Use according to claim 10, wherein the bacteria are selected from gram-negative bacteria, preferably escherichia coli, gram-positive bacteria or methicillin-resistant staphylococcus aureus.
  12. 12. An antibacterial agent comprising the cationic compound according to any one of claims 1 to 6 or the cationic compound produced by the production method according to claim 7 or 8, preferably, the antibacterial agent is a long-acting antibacterial agent.

Description

Cationic compound with long-acting high antibacterial activity and preparation method thereof Technical Field The application belongs to the technical field of antibiosis, and particularly relates to a cationic compound with long-acting high antibacterial activity, and a preparation method and application thereof. Background Bacterial infections and related diseases caused by them have severely affected the quality of life and life safety of humans. Traditional antibiotics against bacterial infections have large side effects, and in recent years abuse of antibiotics has led to an increase in bacterial resistance worldwide and an increasing increase in drug-resistant bacterial infections. World Health Organization (WHO) reports that at least 70 tens of thousands die annually from antibiotic-resistant bacterial disease. The great threat of how to cope with diseases caused by bacterial infections, in particular by drug-resistant strains, to public health safety systems has become a central problem in the biomedical and health fields. Strategies to develop new antibacterial agents and to suggest effective resistance to bacteria caused by prolonged use of antibiotics are leading research hotspots in the field of infectious diseases. The appearance of the antibacterial peptide and the antibacterial metal/metal oxide nano-particles provides a new idea for the research and development of novel antibacterial compounds, but the antibacterial peptide has the advantages of high production cost, high potential toxicity in vivo, sensitivity to environmental conditions such as pH, protease and the like, easy inactivation, high toxicity of the metal/metal oxide nano-particles, and large influence by size, shape and components. A series of disadvantages limit its wide application. Researches show that the cationic polymer has the advantages of i) wide application, simple preparation process and low toxic and side effects, ii) structural designability of a small molecular ionic compound and excellent performance of the polymer, and iii) positive charges of the cationic structure are easy to promote the mutual combination of the cationic polymer and related bacteria. In addition, cationic compounds generally have good water solubility and find wide application in the fields of biology, medicine, chemistry, industry, and the like. With the development of science, the application prospect of the cationic compound is continuously expanded, and the cationic compound is used as a drug delivery carrier, an in-vivo framework material, an in-vivo wetting agent and the like, and is popular in the biological field. The feasibility of developing novel cationic antibacterial compounds is high, and the cationic antibacterial compounds have important significance in the antibacterial field. Disclosure of Invention The application aims to provide a long-acting bactericidal cationic compound which can be applied to daily life and a preparation method thereof. The specific technical scheme is as follows: one aspect of the present application relates to a cationic compound comprising a3, 5-dimethoxyphenoxy group and two quaternary ammonium groups in its molecular structure. Further, the molecular formula of the cationic compound is shown as formula 1, Wherein n is an integer from 2 to 20, m is an integer from 2 to 12, R, R ', R ", R'", R "" are each independently H, any one of F, cl, br, I, NO 2,CF3,OCH3,CN,NH2,COOH,(CH2)x and an aromatic ring, wherein x is selected from integers of 1-20. Further, n=6, 8, 10, 12 or 16 in the formula. Further, m=6 in the formula. Further, in the formula, R is H. Further, in the formula, R, R ', R' are all H. Further, the molecular formula of the cationic compound is shown as formula 2. Another aspect of the application relates to a method for preparing a cationic compound comprising the steps of: dissolving 2, 6-dimethoxy-4-hydroxybenzaldehyde in N, N-dimethylformamide, adding dibromoalkane and potassium carbonate, and purifying after reaction to obtain solid 4-bromoalkoxy-2, 6-dimethoxy benzaldehyde; Dropwise adding benzyl chloride into an acetone solution of tetramethyl alkyl diamine, and reacting to obtain benzyl- (dimethylamino) -dimethyl alkyl amine; Dissolving 4-bromoalkoxy-2, 6-dimethoxy benzaldehyde and benzyl- (dimethylamino) -dimethyl alkylamine in acetonitrile, and purifying after reaction to obtain the cationic compound. Further, in the preparation method, the molar ratio of the 2, 6-dimethoxy-4-hydroxybenzaldehyde to dibromoalkane to the potassium carbonate is 1:2-100:1-10. Further, in the preparation method, the molar ratio of the benzyl chloride to the tetramethyl alkyl diamine is 1:2-100. Further, in the preparation method, the molar ratio of the 4-bromoalkoxy-2, 6-dimethoxy benzaldehyde to benzyl- (dimethylamino) -dimethyl alkylamine is 0.9-1.2:1. Further, in the preparation method, the molecular formula of dibromoalkane is shown as a formula 3, Wherein n is selected from integers from 2 to 20.