CN115650921A - Preparation method and application of imidazole quaternary ammonium salt compound - Google Patents
Preparation method and application of imidazole quaternary ammonium salt compound Download PDFInfo
- Publication number
- CN115650921A CN115650921A CN202211153751.8A CN202211153751A CN115650921A CN 115650921 A CN115650921 A CN 115650921A CN 202211153751 A CN202211153751 A CN 202211153751A CN 115650921 A CN115650921 A CN 115650921A
- Authority
- CN
- China
- Prior art keywords
- quaternary ammonium
- ammonium salt
- imidazole
- preparation
- salt compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title claims abstract description 61
- -1 imidazole quaternary ammonium salt compound Chemical class 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000005303 weighing Methods 0.000 claims abstract description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 20
- 241000894006 Bacteria Species 0.000 abstract description 10
- 125000001424 substituent group Chemical group 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 7
- 210000004369 blood Anatomy 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 6
- 241000233866 Fungi Species 0.000 abstract description 5
- 238000006467 substitution reaction Methods 0.000 abstract description 3
- 150000003384 small molecules Chemical class 0.000 abstract description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 14
- 241000588626 Acinetobacter baumannii Species 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- HNTGIJLWHDPAFN-UHFFFAOYSA-N 1-bromohexadecane Chemical group CCCCCCCCCCCCCCCCBr HNTGIJLWHDPAFN-UHFFFAOYSA-N 0.000 description 7
- 241000228197 Aspergillus flavus Species 0.000 description 7
- 241000228245 Aspergillus niger Species 0.000 description 7
- 241000222122 Candida albicans Species 0.000 description 7
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 7
- 241000228153 Penicillium citrinum Species 0.000 description 7
- 241000222126 [Candida] glabrata Species 0.000 description 7
- 229940095731 candida albicans Drugs 0.000 description 7
- 208000032343 candida glabrata infection Diseases 0.000 description 7
- OSSNTDFYBPYIEC-UHFFFAOYSA-N 1-ethenylimidazole Chemical group C=CN1C=CN=C1 OSSNTDFYBPYIEC-UHFFFAOYSA-N 0.000 description 6
- 230000000845 anti-microbial effect Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 6
- VMKOFRJSULQZRM-UHFFFAOYSA-N 1-bromooctane Chemical group CCCCCCCCBr VMKOFRJSULQZRM-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- MLMGJTAJUDSUKA-UHFFFAOYSA-N 2-ethenyl-1h-imidazole Chemical class C=CC1=NC=CN1 MLMGJTAJUDSUKA-UHFFFAOYSA-N 0.000 description 3
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical class CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 206010018910 Haemolysis Diseases 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000008588 hemolysis Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 description 1
- PUAQLLVFLMYYJJ-UHFFFAOYSA-N 2-aminopropiophenone Chemical compound CC(N)C(=O)C1=CC=CC=C1 PUAQLLVFLMYYJJ-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 1
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000005548 dental material Substances 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000031877 prophase Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method and application of an imidazole quaternary ammonium salt compound. The preparation method comprises the following steps: weighing 20mmol,1eq imidazole molecule and 40mmol,2eq halogenated alkane, adding 30mL dichloromethane into a 100mL round-bottom flask, refluxing for 6-36 hours at 65 ℃, removing the solvent after the reaction is completed, and purifying. The invention can synthesize quaternary ammonium salt compounds containing different substituent groups through simple organic substitution reaction, the lengths of different substituent groups have great influence on the antibacterial performance of the quaternary ammonium salt compounds, when the branched chain has 12 or 16 carbon chains, the quaternary ammonium salt compounds have good antibacterial performance on bacteria, drug-resistant bacteria, fungi and mould, and the quaternary ammonium salt compounds have good blood compatibility and cell compatibility, thereby providing an early-stage basis for seeking small-molecule medicines with good antibacterial performance.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method and application of an imidazole quaternary ammonium salt compound.
Background
Quaternary Ammonium Salts (QAs) are highly stable compounds with excellent transfer catalytic properties and potential antibacterial properties. The potential antimicrobial properties of QAs have prompted their interest in materials where antimicrobial activity is highly desirable, such as blood purification materials, dental materials, and the like. A large number of antimicrobial agents have been reported in the past, such as chlorhexidine, antibiotics, zinc, silver, fluorine, iodine, and the like. Although these antimicrobial agents have good antimicrobial properties, these antimicrobial materials can exert their antimicrobial properties only in a short time, and poor biocompatibility limits further applications. In recent years, the design and synthesis of polymerizable QAs compounds has attracted the eye, and their antibacterial properties depend on the kind of anion, the type and length of the substituent group. Meanwhile, polymerizable QAs can improve biocompatibility and hemocompatibility of QAs by polymerizing different functional monomers. Therefore, it is a great challenge to prepare polymerizable QAs having excellent antibacterial properties by a simple and efficient method, and there is also an urgent need for the method.
The imidazole skeleton is often present in natural antibacterial molecules, and the antibacterial properties of imidazole molecules with different substituent groups are different, and the antibacterial properties of the same imidazole molecule to different bacteria, fungi and moulds thereof are also different. However, there is currently no systematic study on the derivation of different branched imidazoles and their antibacterial properties against different bacteria and their hemocompatibility and cytocompatibility.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a preparation method and application of an imidazole quaternary ammonium salt compound.
In order to achieve the purpose of the invention, the invention adopts the technical scheme that:
the preparation method of the imidazole quaternary ammonium salt compound comprises the following steps:
weighing 20mmol,1eq imidazole molecules, 40mmol,2eq halogenated alkane, adding 30mL dichloromethane into a 100mL round-bottom flask, refluxing for 6-36 hours at 65 ℃, removing the solvent after the reaction is completed, and purifying;
wherein R is 1 Represents CH 3 、C 2 H 3 、Ph；R 2 Represents Cl, br, I; r 3 Represents C4-C20 alkyl, benzyl or cyclopentyl.
The imidazole quaternary ammonium salt compound prepared according to the preparation method is provided, and the branched chain of the imidazole quaternary ammonium salt compound comprises 12 or 16 carbon chains.
Provided is a pharmaceutical composition comprising, as an active ingredient, an imidazole quaternary ammonium salt compound having a branched chain comprising 12 or 16 carbon chains, or a pharmaceutically acceptable salt thereof.
Further, the pharmaceutical composition also comprises pharmaceutically acceptable pharmaceutic adjuvants.
Provides an application of imidazole quaternary ammonium salt compounds with branched chains comprising 12 or 16 carbon chains in the preparation of antibacterial agents.
The beneficial effects of the invention are as follows:
through simple organic substitution reaction, quaternary ammonium salt compounds containing different substituent groups can be synthesized, the length of different substituent groups has great influence on the antibacterial performance of the quaternary ammonium salt compounds, when the branched chain is 12 or 16 carbon chains, the quaternary ammonium salt compounds have good antibacterial performance on bacteria, drug-resistant bacteria, fungi and mould, and the quaternary ammonium salt compounds have good blood compatibility and cell compatibility, so that a prophase basis is provided for seeking small molecular drugs with good antibacterial performance.
Drawings
FIG. 1 is a schematic diagram of the synthesis of imidazole quaternary ammonium salt compounds;
FIG. 2 shows the structure and nuclear magnetic spectrum of imidazole quaternary ammonium salt compound: ( 1 H-NMR); wherein (a) the molecular structure and nuclear magnetic hydrogen spectrum of vinyl imidazole substituted by bromo-hexadecyl alkane; (b) Bromododecyl alkane substituted vinyl imidazole molecular structure and nuclear magnetic hydrogen spectrum; (c) Bromo-n-octane substituted vinyl imidazole molecular structure and nuclear magnetic hydrogen spectrum; (d) Bromohexadecane substituted methylimidazole molecular structure and nuclear magnetic hydrogen spectrum.
Detailed Description
The following description of the embodiments of the present invention is provided to facilitate the understanding of the present invention by those skilled in the art, but it should be understood that the present invention is not limited to the scope of the embodiments, and it will be apparent to those skilled in the art that various changes may be made without departing from the spirit and scope of the invention as defined and defined in the appended claims, and all matters produced by the invention using the inventive concept are protected.
Example 1
20mmol (1 eq) of vinylimidazole and 40mmol (2 eq) of bromohexadecane are weighed into a 100mL round-bottomed flask, 30mL of dichloromethane are added, reflux is carried out at 65 ℃ and the reaction is checked by thin-layer chromatography. After the reaction is completed, removing solvent by using rotary evaporator, utilizing column chromatography technology to obtain product (its purity is greater than 95%), synthesizing bromohexadecane substituted vinyl imidazole derivative, making it pass through nuclear magnetic hydrogen spectrum (C: (C) (C)) 1 H-NMR) and its structure is correct (as shown in figure 2 a).
Example 2
20mmol (1 eq) of vinylimidazole and 40mmol (2 eq) of bromododecane are weighed into a 100mL round-bottomed flask, 30mL of dichloromethane are added, reflux is carried out at 65 ℃ and the reaction is detected by thin layer chromatography. After the reaction is completed, removing solvent by using rotary evaporator, utilizing column chromatography technology to obtain product (its purity is greater than 95%), synthesizing bromododecaalkane substituted vinyl imidazole derivative, making nuclear magnetic hydrogen spectrum (A), (B) and (C) 1 H-NMR), its structure is correct (as shown in figure 2 b).
Example 3
20mmol (1 eq) of vinylimidazole and 40mmol (2 eq) of bromo-n-octane are weighed into a 100mL round-bottomed flask, 30mL of dichloromethane are added, reflux is carried out at 65 ℃, and the reaction is detected by thin layer chromatography. After the reaction is completed, removing solvent by using a rotary evaporator, obtaining a product (the purity is more than 95%) by using a column chromatography technology, synthesizing bromo-n-octane substituted vinyl imidazole derivative, and performing nuclear magnetic hydrogen spectrum (C/H) 1 H-NMR), its structure is correct (as shown in figure 2 c).
Example 4
Weighing 20mmol (1 eq) of methylimidazole and 40mmol (2 eq) of bromohexadecane in a 100mL round-bottom flask, adding 30mL of dichloromethane, refluxing at 65 ℃, detecting the reaction by using a thin-layer chromatography technology, removing the solvent by using a rotary evaporator after the reaction is completed, obtaining a product (the purity is more than 95%) by using a column chromatography technology, synthesizing the bromohexadecane substituted methylimidazole derivative, and performing nuclear magnetic hydrogen spectrometry (NMR) 1 H-NMR), its structure is correct (as shown in fig. 2 d).
Example 5
The products prepared in examples 1 to 4 were prepared into physiological saline solutions of imidazole quaternary ammonium salts of different concentrations, and staphylococcus aureus (a clinically isolated strain in the xijing hospital), staphylococcus aureus MDR (a clinically isolated strain in the xijing hospital), escherichia coli MDR (a clinically isolated strain in the xijing hospital), acinetobacter baumannii (a clinically isolated strain in the xijing hospital of the university of the four-chuan), acinetobacter baumannii MDR (a clinically isolated strain in the xijing hospital of the university of the four-chuan), candida glabrata (bn36583), candida albicans (the research center for labor-saving microorganism engineering technology in south river, 18638), cryptococcus (the shanghai probiotic, ATCC 32609), aspergillus niger (environmental isolation, identification of strains by the shanghai biotechnology limited), aspergillus flavus (environmental isolation, identification of the shanghai biotechnology limited), penicillium citrinum (the management center for forestry microorganism strain collection 34 in china, turbidity observation of bacterial solutions, and testing of antimicrobial concentrations of different substituted groups (MIC); wherein MICs of the bromohexadecane substituted vinyl imidazole quaternary ammonium salt to staphylococcus aureus, staphylococcus aureus MDR, escherichia coli MDR, acinetobacter baumannii MDR, candida glabrata, candida albicans, cryptococcus, aspergillus niger, aspergillus flavus and penicillium citrinum are respectively as follows: 2.0, 1.0, 7.8, 15.6, 3.9, 2, 1, 0.5, 3.9 μ g/mL; the MICs of the bromododecyl alkane substituted vinyl imidazole quaternary ammonium salt on staphylococcus aureus, staphylococcus aureus MDR, escherichia coli MDR, acinetobacter baumannii MDR, candida glabrata, candida albicans, cryptococcus, aspergillus niger, aspergillus flavus and penicillium citrinum are respectively as follows: 7.8, 3.9, 62.5, 31.3, 3.9, 31.3, 2, 62.5, 15.6 μ g/mL; the MICs of the bromo-n-octane substituted vinyl imidazole quaternary ammonium salt to staphylococcus aureus, staphylococcus aureus MDR, escherichia coli MDR, acinetobacter baumannii MDR, candida glabrata, candida albicans, cryptococcus, aspergillus niger, aspergillus flavus and penicillium citrinum are respectively as follows: 250. 250, 1000, 500, 250, 125, 1000 μ g/mL; the bromo-hexadecyl alkane substituted methyl imidazole quaternary ammonium salt has similar antibacterial effect with the bromo-hexadecyl alkane substituted vinyl imidazole quaternary ammonium salt.
Different bacterial solutions of different imidazole quaternary ammonium salts with the concentration of (10) were prepared by the same method 6 To the power), followed by agar plating, and when the number of colonies is less than 5, the lowest bactericidal concentration (MBC) of the molecule under the conditions is recorded. The results show that different substituents have great influence on the antibacterial performance, and when the branched chains have 12 and 16 carbon chains, the antibacterial performance on the bacteria, the drug-resistant bacteria, the fungi and the mold is better. Wherein the MBC of the bromohexadecane substituted vinyl imidazole quaternary ammonium salt to staphylococcus aureus, staphylococcus aureus MDR, escherichia coli MDR, acinetobacter baumannii MDR, candida glabrata, candida albicans, cryptococcus, aspergillus niger, aspergillus flavus and penicillium citrinum is respectively 7.8, 2, 15.6, 3.9, 7.8, 31.3, 2, 62.5, 3.9 and 3.9 mu g/mL; the MBC of the bromododecyl alkane substituted vinyl imidazole quaternary ammonium salt to staphylococcus aureus, staphylococcus aureus MDR, escherichia coli MDR, acinetobacter baumannii MDR, candida glabrata, candida albicans, cryptococcus, aspergillus niger, aspergillus flavus and penicillium citrinum is 15.6, 3.9, 62.5, 31.3, 62.5, 3.9, 2, 62.5, 125 and 15.6 mu g/mL respectively; the MBC of the bromo-n-octane substituted vinyl imidazole quaternary ammonium salt to staphylococcus aureus, staphylococcus aureus MDR, escherichia coli MDR, acinetobacter baumannii MDR, candida glabrata, candida albicans, cryptococcus, aspergillus niger, aspergillus flavus and penicillium citrinum is 250, 500, 250, 1000, 2000, 250, 125, 1000, 2000 and 1000 mu g/mL respectively.
Example 6
Physiological saline solution (1024, 512, 256, 128, 64, 32, 16, 8, 4, 2, 1 and 0.5 mu g/mL) of imidazole quaternary ammonium salt with different concentrations is prepared, fresh blood is collected, red blood cells are separated out and tested for blood compatibility, red blood cells diluted by physiological saline are used as negative control, and red blood cells diluted by deionized water are used as positive control. The results show that different substituents have a strong influence on hemolysis, and that hemolysis does not occur even when the branched chain is benzyl, cyclopentyl, octyl at a concentration of 1024. Mu.g/mL.
Physiological saline solutions of imidazole quaternary ammonium salts with different concentrations are prepared, and the cell compatibility of the imidazole quaternary ammonium salts is evaluated by using CCK8 cells. The results show that at lower concentrations, the imidazole quat molecules do not have a significant effect on cell growth.
The invention can synthesize quaternary ammonium salt compounds containing different substituent groups through simple organic substitution reaction, the lengths of different substituent groups have great influence on the antibacterial performance of the quaternary ammonium salt compounds, when the branched chain has 12 or 16 carbon chains, the quaternary ammonium salt compounds have good antibacterial performance on bacteria, drug-resistant bacteria, fungi and mould, and the quaternary ammonium salt compounds have good blood compatibility and cell compatibility, thereby providing an early-stage basis for seeking small-molecule medicines with good antibacterial performance.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Any reference sign in a claim should not be construed as limiting the claim concerned.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.
Claims (5)
1. The preparation method of the imidazole quaternary ammonium salt compound is characterized by comprising the following steps:
weighing 20mmol,1eq imidazole molecules, 40mmol,2eq halogenated alkane, adding 30mL dichloromethane into a 100mL round-bottom flask, refluxing for 6-36 hours at 65 ℃, removing the solvent after the reaction is completed, and purifying;
wherein R is 1 Represents CH 3 、C 2 H 3 、Ph；R 2 Represents Cl, br, I; r 3 Represents C4-C20 alkyl, benzyl or cyclopentyl.
2. An imidazole quaternary ammonium salt compound prepared by the preparation method according to claim 1, characterized in that: the branched chain comprises 12 or 16 carbon chains.
3. A pharmaceutical composition comprising the imidazole quaternary ammonium salt compound or a pharmaceutically acceptable salt thereof according to claim 2 as an active ingredient.
4. The pharmaceutical composition of claim 3, further comprising a pharmaceutically acceptable pharmaceutical excipient.
5. The use of imidazole quats according to claim 2 in the preparation of antibacterial agents.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211153751.8A CN115650921A (en) | 2022-09-21 | 2022-09-21 | Preparation method and application of imidazole quaternary ammonium salt compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211153751.8A CN115650921A (en) | 2022-09-21 | 2022-09-21 | Preparation method and application of imidazole quaternary ammonium salt compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115650921A true CN115650921A (en) | 2023-01-31 |
Family
ID=85024584
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211153751.8A Pending CN115650921A (en) | 2022-09-21 | 2022-09-21 | Preparation method and application of imidazole quaternary ammonium salt compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115650921A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102870781A (en) * | 2012-09-18 | 2013-01-16 | 浙江大学 | Imidazolium macromolecular antimicrobial agent and preparation method thereof |
| CN104073899A (en) * | 2014-06-25 | 2014-10-01 | 杭州师范大学 | Application of ionic liquid in polylactic acid composite fibers |
| CN113234017A (en) * | 2021-05-21 | 2021-08-10 | 天津包钢稀土研究院有限责任公司 | Imidazole salt compound with antibacterial effect and preparation method and application thereof |
-
2022
- 2022-09-21 CN CN202211153751.8A patent/CN115650921A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102870781A (en) * | 2012-09-18 | 2013-01-16 | 浙江大学 | Imidazolium macromolecular antimicrobial agent and preparation method thereof |
| CN104073899A (en) * | 2014-06-25 | 2014-10-01 | 杭州师范大学 | Application of ionic liquid in polylactic acid composite fibers |
| CN113234017A (en) * | 2021-05-21 | 2021-08-10 | 天津包钢稀土研究院有限责任公司 | Imidazole salt compound with antibacterial effect and preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| D. DEMBERELNYAMBA等: "Synthesis and antimicrobial properties of imidazolium and pyrrolidinonium salts", 《BIOORGANIC & MEDICINAL CHEMISTRY》, vol. 12, pages 854 * |
| ZHIQIANG ZHENG等: "Structure−Antibacterial Activity Relationships of Imidazolium-Type Ionic Liquid Monomers, Poly(ionic liquids) and Poly(ionic liquid) Membranes: Effect of Alkyl Chain Length and Cations", 《ACS APPLIED MATERIALS & INTERFACES》, vol. 8, no. 20, pages 12684 * |
| 潘帅: "新型高分子抗菌剂的合成与性能研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》, no. 6, pages 20 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108752501B (en) | Organic acid salt-containing chitosan quaternary ammonium salt and preparation method and application thereof | |
| CN107094765B (en) | Quaternary ammonium salt modified chitosan microsphere and preparation method and application thereof | |
| CN105061632B (en) | The preparation method and bacteriostasis property of a kind of curdlan quaternary ammonium salt | |
| CN107163160B (en) | A kind of Ascorbic acid chitosan quaternary ammonium salt and preparation method thereof | |
| Bhattacharjee et al. | Cadmium (II) coordination polymer based on flexible dithiolate-polyamine binary ligands system: crystal structure, Hirshfeld surface analysis, antimicrobial, and DNA cleavage potential | |
| CN110776551A (en) | Polymerizable rosin quaternary ammonium salt bactericide, preparation method thereof and polymerized rosin quaternary ammonium salt bactericide prepared from polymerizable rosin quaternary ammonium salt bactericide | |
| CN115650921A (en) | Preparation method and application of imidazole quaternary ammonium salt compound | |
| Kondratenko et al. | Contribution of the Scientific School of Academician MG Voronkov to the Development of the Chemistry of Biologically Active Atranes (Protatranes and Hydrometallatranes)(A Review) | |
| Vorob’eva et al. | Synthesis and biological properties of copolymers based on N, N-diallyl-N, N-dimethylammonium chloride | |
| WO2023131355A1 (en) | Water-soluble chlorhexidine antibacterial, preparation method therefor and application thereof | |
| CN115304528B (en) | Degradable gemini quaternary ammonium salt, preparation method thereof and bactericide | |
| CN109305988A (en) | Ciprofloxacin metal complex and its preparation method and application | |
| Inoue et al. | Antibacterial characteristics of newly developed amphiphilic lipids and DNA–lipid complexes against bacteria | |
| EP3013842B1 (en) | Novel method for synthesising n-alkyl-glycosyl(di)amine derivatives and uses of same against phytopathogens | |
| CN105463439A (en) | Rhodium-complex-modified titanium material and preparing method and application of rhodium-complex-modified titanium material | |
| CN111228276A (en) | Bromooxamide binuclear copper complex with antibacterial activity and composition thereof | |
| EP1892236B1 (en) | Iodide salts of dimethylaminoethanol fatty acid esters with bacteriostatic, mycostatic, yeaststatic and/or microbicide activity for use in cleansing or purifying formulations | |
| CN111848656B (en) | Ion-modified protoporphyrin gallium compound and preparation method and application thereof | |
| US3338906A (en) | Quaternary ammonium salts of substituted phenanthrolines | |
| CN115583978B (en) | Phenazine ruthenium (II) complex hexafluorophosphate for inhibiting cryptococcus, and preparation method and application thereof | |
| CN117447373A (en) | Preparation of methionine derivative and its salts and use as antibacterial agent | |
| KR102162475B1 (en) | Branched dicarboxylic compound having anhydrosugar alcohol core and alkylene oxide extender and method for preparing the same | |
| AU2018100501A4 (en) | Naproxen sodium drug intermediates 2-ethoxynaphthaloic acid synthesis method | |
| CN102206191B (en) | 1, 4-bis (4-amino-5-mercapto-1, 2, 4-triazole)-benzene, its preparation method and application | |
| CN107753947B (en) | Imidazole ionic liquid photosensitizer and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information |
Inventor after: Jin Lunqiang Inventor after: Su Baihai Inventor after: Deng Ningyue Inventor before: Jin Lunqiang |
|
| CB03 | Change of inventor or designer information |