Anti-drug-resistance antibacterial amidine oligomer as well as preparation method and application thereof

A production method and oligomerization-like technology, applied in antibacterial drugs, resistance to vector-borne diseases, organic chemistry, etc., can solve problems such as high toxicity, and achieve the effect of low toxicity, high therapeutic index, and broad-spectrum antibacterial activity

Active Publication Date: 2021-12-07
HUNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In order to solve the problem of high toxicity of traditional high-molecular-weight antibacterial polymers, the i

Method used

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  • Anti-drug-resistance antibacterial amidine oligomer as well as preparation method and application thereof
  • Anti-drug-resistance antibacterial amidine oligomer as well as preparation method and application thereof
  • Anti-drug-resistance antibacterial amidine oligomer as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] After testing, a kind of antibacterial amidine oligomer with broad-spectrum antibacterial property, its chemical formula is as follows:

[0032]

[0033] Wherein, 5≤n≤8, R1 and R2 have the structure in the above description. It can be seen from the above structural formula that 81 compounds can be obtained through different combinations of R1 and R2. In order to facilitate the analysis and description of these compounds, 60 compounds are labeled in Table 1 below. It should be noted that, For those skilled in the art, unlabeled compounds can also be synthesized, and the properties and synthesis methods of these unlabeled compounds are similar to those of the 60 labeled compounds, so no further analysis and description are made in the present invention.

[0034] The structural formulas of the 60 compounds and their antibacterial activities and biocompatibility lists are shown in Table 1 and Table 2. It can be seen from Table 2 that, compared with other compounds, the t...

Embodiment 2

[0041] As shown in Figure 1, the present invention also discloses a method for synthesizing an antibacterial amidine oligomer with drug resistance, comprising the steps of:

[0042] S1: prepare a compound monomer with the following molecular formula:

[0043]

[0044] S2: react the compound monomer with H2N-R2-NH2, anhydrous N,N-dimethylformamide (DMF) and N,N-diisopropylethylamine (DIPEA) to obtain the amidines The oligomers, R1 and R2 have the structures described above.

[0045] Wherein, the above step S1 includes the following steps:

[0046] S11: Weigh 5-cyanindole or 6-cyanindole and di-tert-butyl dicarbonate, then add dichloromethane and mix evenly, add a catalytic amount of 4-dimethylaminopyridine (DMAP) at 2-6 After stirring at ℃ for half an hour, return to room temperature of 20-25℃ and stir overnight, filter and wash the mixture and spin dry with a rotary evaporator to obtain a solid product, and then purify the product with a silica gel column to obtain a whit...

experiment example 1

[0053] This experimental example is described in detail with the P2 compound:

[0054] Materials and methods: All reagents were provided by TCI (USA), Sigma-Aldrich, McLean, Adamas and other organic reagent companies and Beyontian Biotechnology Co., Ltd., and were used directly without further purification (unless otherwise specified). The ultrapure water used in the experiment came from a Milli-Q purification instrument. The inert gas is nitrogen.

[0055] Synthesis of P2 The synthesis steps are shown in Figure 1. Carry on the synthesis of 4',6-diimido-2-phenylindole hydrochloride monomer firstly. Weigh 6-cyanindole (10g, 70.3mmol) and di-tert-butyl dicarbonate (BOC) (35.36g, 162mmol), then add 100mL of dichloromethane and mix well, then add a catalytic amount of 4-dimethylamino Pyridine (DMAP) (0.86g, 7.03mmol), stirred at room temperature for 12-24h to obtain a mixture, the mixture was extracted and spin-dried to obtain a solid mixture, and the solid mixture was separate...

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Abstract

The invention discloses an anti-drug-resistance antibacterial amidine oligomer, a preparation method, application and an antibacterial mechanism of the antibacterial amidine oligomer, and an application of the antibacterial amidine oligomer in sterilization in an intracellular infection model and a zebra fish model infected by mycobacterium fortuitum. The antibacterial types of the amidine oligomer comprise escherichia coli, enterococcus faecalis, staphylococcus aureus, klebsiella pneumoniae, acinetobacter baumannii, pseudomonas aeruginosa, mycobacterium smegmatis, mycobacterium fortuitum and the like. The structure disclosed by the invention has double antibacterial mechanisms of destroying bacterial cell membranes and combining chromosome DNA, has the characteristics of rapid sterilization and drug resistance, and shows antibacterial broad spectrum. In addition, the structure has low toxicity to blood cells, and has high safety in blood. Meanwhile, the structure can be applied to a Raw264.7 cell model infected by mycobacterium smegmatis and mycobacterium fortuitum, and the structure also has a good treatment effect on the zebra fish model infected by MRSA and mycobacterium fortuitum.

Description

technical field [0001] The invention relates to the field of pharmaceutical and chemical materials, and more specifically relates to an antibacterial amidine oligomer with drug resistance and its preparation method and application. Background technique [0002] The abuse of antibiotics in the antibacterial field has accelerated the emergence of drug-resistant strains and multidrug-resistant strains. Bacterial drug resistance has become a common and serious problem that endangers human health. Therefore, it is extremely urgent to develop new antibacterial agents that can quickly kill drug-resistant bacteria without causing bacterial drug resistance. Recently, the concept of anti-drug-resistant antibacterial agents has been established, aiming to solve the problem of bacterial resistance by designing a cationic amidine antibacterial oligomer with dual antibacterial mechanisms. [0003] The amidine anti-drug resistance antibacterial agent with dual antibacterial mechanism shou...

Claims

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Application Information

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IPC IPC(8): C07C257/18C07D209/18A61P31/04
CPCC07D209/18A61P31/04C07D295/13C07C323/25C07C257/18Y02A50/30
Inventor 冯欣欣白玉罡王建雪陈先会陈亚杰
Owner HUNAN UNIV
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