CN110615777A - Compound and preparation method and application thereof - Google Patents

Compound and preparation method and application thereof Download PDF

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Publication number
CN110615777A
CN110615777A CN201910766924.5A CN201910766924A CN110615777A CN 110615777 A CN110615777 A CN 110615777A CN 201910766924 A CN201910766924 A CN 201910766924A CN 110615777 A CN110615777 A CN 110615777A
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compound
formula
alkyl
aryl
cooh
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宋凌杰
王向红
闫顺杰
栾世方
殷敬华
石恒冲
杨华伟
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Changchun Institute of Applied Chemistry of CAS
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Changchun Institute of Applied Chemistry of CAS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/92—Naphthofurans; Hydrogenated naphthofurans
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1003—Carbocyclic compounds
    • C09K2211/1007—Non-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
    • C09K2211/10—Non-macromolecular compounds
    • C09K2211/1018—Heterocyclic compounds
    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom

Abstract

The invention provides a compound and a preparation method and application thereof, the compound with the structure of formula (I) provided by the invention selects a specific structure, and experiments show that the compound can be detected in real time by a fluorescence technology and has the advantages of high detection sensitivity, quick detection, good biocompatibility and the like; and the antibacterial compound can realize controllable, broad-spectrum and efficient sterilization function while quickly diagnosing bacterial infection, is an antibacterial compound integrating diagnosis and treatment functions, and has wide application prospect in the anti-infection medical field.

Description

Compound and preparation method and application thereof
Technical Field
The invention relates to the technical field of medicines, and particularly relates to a compound and a preparation method and application thereof.
Background
Bacterial infections can cause about one third of the world's fatality, posing a serious threat to public health worldwide. In recent years, the situation of global bacterial infections has been further exacerbated by problems such as bacterial resistance due to improper use and abuse of antibiotics. The early and rapid bacterial infection diagnosis is convenient for timely obtaining the bacterial infection condition and is beneficial to timely taking effective treatment measures, the treatment difficulty of infectious diseases can be greatly reduced, the treatment time is shortened, and the treatment effect is improved. Although a variety of well-established techniques (e.g., standard plate counting and polymerase chain reaction) have been used for accurate bacterial detection to date, these methods are often time consuming, cumbersome to operate, and highly dependent on sophisticated equipment and skilled technicians, greatly limiting their use for rapid detection. In contrast, fluorescence technology offers an attractive option for rapid and reliable bacterial detection by virtue of the advantages of real-time detection, high sensitivity, non-invasiveness and economy.
Currently, the bacterial diagnosis and treatment process are independent in clinical application, and the time interval from diagnosis to treatment process is long, which inevitably delays the optimal treatment time, reduces the treatment effect and increases the economic and psychological burden of patients. Thus, "personalized" treatment strategies that effectively combine diagnosis and treatment have become a focus of research in recent years. However, most of the developed diagnosis and treatment antibacterial systems are function integration of multiple materials, the preparation process is complicated, the process difficulty is high, and some systems belong to non-broad-spectrum sterilization or are easy to generate bacterial drug resistance. Therefore, how to realize the simple and effective integration of diagnosis and inactivation of bacteria, especially drug-resistant bacteria, is a research hotspot and difficulty in current research on bacterial infection resistance.
Disclosure of Invention
In view of the above, the technical problem to be solved by the present invention is to provide a compound, a preparation method and an application thereof, wherein the compound provided by the present invention can realize rapid and non-invasive bacterial detection on broad spectrum bacteria and simultaneously realize efficient inactivation on the broad spectrum bacteria.
The invention provides a compound, which has a structure shown in a formula (I):
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R1is selected fromWherein R is4Is selected from C1-C18Alkyl of (3) or aryl of C6-C50, R5、R6Independently selected from-H and C1-C18Alkyl groups of (a);
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C20, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C20, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
Preferably, said R is2Selected from alkyl of-H, C3-C12, aryl of C6-C30, -OH, alkoxy of C3-C12, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
Preferably, said R is3Selected from alkyl of-H, C3-C12, aryl of C6-C30, -OH, alkoxy of C3-C12, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
Preferably, said R is4Selected from-H, C3-C12 alkyl or C6 ℃Aryl of C30.
Preferably, said R is5、R6Independently selected from-H or C3-C12 alkyl.
The invention provides a preparation method of the compound, which comprises the following steps:
1) mixing the compound with the structure of the formula (II) and the compound with the structure of the formula (III) for reaction to obtain the compound with the structure of the formula (IV),
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br;
2) converting the compound with the structure of the formula (IV) into a compound with the structure of the formula (I);
wherein R is1Is selected fromWherein R is4Is selected from C1-C18Alkyl of (3) or aryl of C6-C50, R5、R6Independently selected from-H and C1-C18Alkyl group of (1).
The invention provides application of a compound with a structure shown in a formula (I) in preparation of a medicine or a device integrating bacterial diagnosis and treatment.
The invention also provides a medicament integrating bacterial diagnosis and treatment, which comprises the following components: the compound with the structure of formula (I) and pharmaceutically acceptable auxiliary materials;
wherein the auxiliary material is one or more of a solvent, an auxiliary agent and a carrier.
The invention also provides a photosensitive antibacterial drug which has a structure shown in a formula (IV),
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -C1 or-Br.
Preferably, the photosensitive wavelength of the photosensitive antibacterial drug is 300-1100 nm.
Compared with the prior art, the compound with the structure shown in the formula (I) selects a specific structure, and experiments show that the compound can detect bacteria in real time by a fluorescence technology and has the advantages of high detection sensitivity, high detection speed, good biocompatibility and the like; and the antibacterial compound can realize controllable, broad-spectrum and efficient sterilization function while quickly diagnosing bacterial infection, is an antibacterial compound integrating diagnosis and treatment functions, and has wide application prospect in the anti-infection medical field.
Drawings
FIG. 1 is a schematic diagram of CORM and CORM-Ac structure and synthesis;
FIG. 2 is a diagram of CORM1HNMR spectrogram;
FIG. 3 is an ESI-MS spectrum of CORM;
FIG. 4 is of CORM-Ac1HNMR spectrogram;
FIG. 5 is an ESI-MS spectrum of CORM-Ac;
FIG. 6 shows the CO release of CORM;
FIG. 7 is a graph showing the change of fluorescence color of a molecular solution before and after invasion of gram-positive bacteria (Staphylococcus aureus), negative bacteria (Escherichia coli), and drug-resistant bacteria (methicillin-resistant Staphylococcus aureus);
FIG. 8 is a plate diagram of the coating of the solution of gram-positive bacteria, gram-negative bacteria and drug-resistant bacteria without adding the antibacterial flavonoid molecules in the dark;
FIG. 9 is a plate diagram of the application of the anti-microbial flavonoid molecules, gram-positive bacteria, gram-negative bacteria and drug-resistant bacteria solution in the dark;
FIG. 10 is a flat chart of a solution coating of gram-positive bacteria, gram-negative bacteria and drug-resistant bacteria without adding antibacterial flavonoid molecules under illumination;
FIG. 11 is a plate diagram of a solution coating of light plus antimicrobial flavonoid molecules, gram-positive bacteria, gram-negative bacteria, and drug-resistant bacteria.
Detailed Description
The invention provides a compound, which has a structure shown in a formula (I):
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R1is selected fromWherein R is4Is selected from C1-C18Alkyl of (3) or aryl of C6-C50, R5、R6Independently selected from-H and C1-C18Alkyl groups of (a);
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2、-F、-Cl or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
According to the invention, said R2Preferably an alkyl group of-H, C3 to C12, an aryl group of C6 to C30, -OH, an alkoxy group of C3 to C12, -COOH, -NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br, more preferably-H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, n-octyl, n-decyl, phenyl, naphthyl, anthryl, phenanthryl, -OH, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy, isopentoxy, n-hexoxy, n-heptoxy, n-octoxy, n-decoxy, -COOH, -NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
According to the invention, R3 is preferably an alkyl group of-H, C3-C12, an aryl group of C6-C30, -OH, an alkoxy group of C3-C12, -COOH, -NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br, more preferably-H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, n-octyl, n-decyl, phenyl, naphthyl, anthryl, phenanthryl, -OH, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy, isopentoxy, n-hexoxy, n-heptoxy, n-octoxy, n-decoxy, -COOH, -NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
According to the invention, said R4Preferably an alkyl group of-H, C3 to C12 or an aryl group of C6 to C30, more preferably-H, methyl, ethyl, n-propyl, isopropyl, n-butylAn alkyl group, an isobutyl group, a tert-butyl group, a n-pentyl group, an isopentyl group, a n-hexyl group, a n-heptyl group, a n-octyl group, a n-decyl group, a phenyl group, a naphthyl group, an anthryl group or a phenanthryl group.
According to the invention, R5 is preferably-H or C3-C12 alkyl, more preferably-H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, n-octyl or n-decyl.
According to the invention, said R6preferably-H or an alkyl group of C3 to C12, more preferably-H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, n-octyl or n-decyl.
More specifically, the compounds are specifically as follows:
the invention also provides a preparation method of the compound, which comprises the following steps:
mixing the compound with the structure of the formula (II) and the compound with the structure of the formula (III) for reaction to obtain the compound with the structure of the formula (IV),
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br;
converting the compound with the structure of the formula (IV) into a compound with the structure of the formula (I);
wherein R is1Is selected fromWherein R is4Is selected from C1-C18Alkyl of (3) or aryl of C6-C50, R5、R6Independently selected from-H and C1-C18Alkyl group of (1).
According to the invention, the compound with the structure of formula (II) and the compound with the structure of formula (III) are mixed and reacted to obtain the compound with the structure of formula (IV), wherein, the invention has no special requirement on the reaction conditions and the dosage of each raw material, and a person skilled in the art can select a proper preparation process according to the existing preparation method of similar compounds.
According to the invention, the compound with the structure of formula (IV) is converted into the compound with the structure of formula (I); the reaction conditions and the amounts of the raw materials are not particularly required in the present invention, and those skilled in the art can select a suitable preparation process according to the existing preparation method of similar compounds.
The invention also provides application of the compound with the structure shown in the formula (I) in preparation of a medicine or a device integrating bacterial diagnosis and treatment.
The invention also provides a medicament integrating bacterial diagnosis and treatment, which comprises the following components: the compound with the structure of formula (I) and pharmaceutically acceptable auxiliary materials;
the auxiliary material is one or more of a solvent, an auxiliary agent and a carrier, and more specifically, the solvent is preferably one or more of water, methanol, ethanol, acetonitrile, acetic acid, acetone, chloroform, DMSO, DMF and THF; the carrier is one or more of polyethylene, polypropylene, polystyrene, polyvinyl alcohol, polycarbonate and polyurethane; the carrier is in the form of a flat membrane, non-woven fabric, hydrogel, rubber or elastomer; when the medicine is a compound with a structure shown in a formula (I) and a solvent, the medicine concentration of the compound with the structure shown in the formula (I) in the medicine is 1-1000 mu g/mL; when the drug is a carrier drug, the compound with the structure of the formula (I) is loaded on the carrier by methods such as dip coating, spray coating, blending, adsorption, grafting and the like.
The invention also provides a photosensitive antibacterial drug which has a structure shown in a formula (IV),
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
Wherein the photosensitive wavelength of the photosensitive antibacterial drug is 300-1100nm, and more preferably 300-900 nm; the illumination power is 0.01W-100W, and the illumination time is 0-24 h.
Experiments show that the compound with the structure shown in the formula (I) can generate a rapid change of fluorescence color in the presence of bacteria, and can be further used for indicating bacterial infection, and the concentration of infected bacteria can be determined according to the change of fluorescence intensity; through a light irradiation administration system, the compound is found to generate carbon monoxide (CO) gas with broad-spectrum bactericidal property, and gram-positive bacteria, gram-negative bacteria and drug-resistant bacteria can be killed; thereby realizing the integration of diagnosis and treatment of bacteria.
The following will clearly and completely describe the technical solutions of the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A preparation method of a diagnosis and treatment integrated antibacterial molecular formula (I-1) (CORM-Ac) comprises the following steps of (1) reacting, wherein the reaction process is shown in figure 1, and figure 1 is a schematic diagram of the structure and synthesis of CORM and CORM-Ac; the specific synthesis process is as follows:
synthesis of 3-hydroxy-2-phenyl-4H-benzo [ H ] chromen-4-one (CORM, FIG. 1A): benzaldehyde (5mmol), 1 '-hydroxy-2' -acetylacetone (5mmol) and potassium hydroxide (25%, 15ml) were added to ethanol (40ml), and the mixture was stirred at room temperature for 15 hours. Then hydrogen peroxide (5ml, 30%) was added and the mixture was stirred at room temperature for an additional 12 h. After the reaction was completed, the mixture was poured into ice water and acidified with dilute hydrochloric acid. The resulting yellow-brown precipitate was filtered off and washed with water, and the crude product was recrystallized from ethanol in about 52% yield.
The structure of the obtained product was identified, and the results are shown in FIGS. 2 to 3, and FIG. 2 is that of CORM1HNMR spectrogram; FIG. 3 is an ESI-MS spectrum of CORM; as can be seen from the figure:1h NMR (DMSO-d6, 300MHz,) δ 9.88(S, 1H), 8.68(d d, J ═ 6.1, 3.3Hz, 1H), 8.35(d, J ═ 7.5Hz, 2H), 8.14(dd, J ═ 6.1, 3.1Hz, 1H), 8.07(d, J ═ 8.7Hz, 1H), 7.93(d, J ═ 8.8Hz, 1H), 7.84(dd, J ═ 6.2, 3.2Hz, 2H), 8.68(dd, J ═ 6.1, 3.1, 3Hz, J ═ 6.1, 3.3Hz, 1H), 8.68(d, J ═ 6.1, 3.1, 31H). Product ESI-MS: c19H13O3[MH]+：289.3。
Synthesis of 4-oxo-2-phenyl-4H-benzol [ H ] chromen-3-y1 acetate 4-oxo-2-phenyl-4H-benzo [ H ] chromen-3-yl acetate (CORM-Ac):
CORM (5mmol) and acetic anhydride (25 mmol) were dissolved in THF (40ml) and 4-dimethylaminopyridine (DMAP, 0.08 mmol) was added as a catalyst. After stirring at room temperature for 18 hours, the resulting mixture was poured into water, and a white precipitate was obtained by filtration (about 60%) as a compound having the structure of formula (I-1).
The structure of the obtained compound is identified, and the results are shown in FIGS. 4-5, and FIG. 4 shows that of CORM-Ac1HNMR spectrogram; FIG. 5 is an ESI-MS spectrum of CORM-Ac; as can be seen from the figures, it is,1h NMR (DMSO-d6, 300MHz,): δ 8.63(d, j ═ 8.7Hz, 1H), 8.18(d, ═ 7.5Hz, 1H), 8.08-8.02(m, 4H), 7.89-7.82(m, 2H), 7.68(m, 3H), 2.38(s, 3H). Product ESI-MS: c21H15O4[MH]+：331.4。
The obtained compound CORM was tested for CO release: measured using a commercial CO detector. The method comprises the following specific steps: CORM was dissolved in acetonitrile to prepare a 1mg/mL solution. 1mL of this solution was placed in a 20mL Agilent vial and sealed by oxygenation. After subsequent 12h of continuous irradiation of the vial with simulated daylight (37500lx), CO was detected using a commercial CO detector, as shown in fig. 6, fig. 6 showing CO evolution of CORM, wherein (a) CORM was irradiated for 12h, (b) CORM was not irradiated, and (c) acetonitrile solution was irradiated for 12 h.
Example 2
Selecting Staphylococcus aureus as representative gram positive bacteria, adding 30 μ g/mL compound solution (CORM-Ac/DMSO solution) of formula (I-1) into 106cells/mL staphylococcus aureus suspension, after shaking and incubation for 30min, fluorescence images of the suspension were taken by a digital camera under the irradiation of a portable ultraviolet lamp (365nm), and the results are shown in FIG. 7.
Example 3
Selecting Escherichia coli as representative gram negative bacteria, adding 30 μ g/mL compound solution (CORM-Ac solution/DMSO) of formula (I-1) into 106After shaking and incubating the cells/mL Escherichia coli suspension for 30min, a fluorescence image of the suspension was taken by a digital camera under the irradiation of a portable ultraviolet lamp (365nm), and the result is shown in FIG. 7.
Example 4
Selecting methicillin-resistant staphylococcus aureus as representative drug-resistant bacteria, adding 30 μ g/mL compound solution (CORM-Ac/DMSO solution) of formula (I-1) into 106cells/mL methicillin-resistant staphylococcus aureus suspension, oscillating and incubating for 30min, and passing through a portable ultraviolet lamp (365nm) under irradiationThe digital camera takes a fluorescence image of the suspension and the results are shown in fig. 7.
Comparative example 1
An equal amount of DMSO solvent without the compound of formula (I-1) (CORM-Ac) was added to 106cells/mL of Staphylococcus aureus suspension, after shaking and incubation for 30min, and storing in the dark for 30min, a certain amount of the bacterial suspension was spread on LB agar plates and incubated at 37 ℃, and bacterial activity was evaluated by counting the number of viable bacterial colonies, and the results are shown in FIG. 8.
Comparative example 2
An equal amount of DMSO solvent without the compound of formula (I-1) (CORM-Ac) was added to 106cells/mL E.coli suspension, after incubation with shaking for 30min, and storage in the dark for 30min, a certain amount of the bacterial suspension was spread on LB agar plates and incubated at 37 ℃ and bacterial activity was evaluated by counting the number of viable bacterial colonies, and the results are shown in FIG. 8.
Comparative example 3
An equal amount of DMSO solvent without the compound of formula (I-1) (CORM-Ac) was added to 106cells/mL methicillin-resistant Staphylococcus aureus suspension, after shaking and incubating for 30min, storing in the dark for 30min, spreading a certain amount of the bacterial suspension on LB agar plates, incubating at 37 ℃, and evaluating the bacterial activity by counting the number of viable bacterial colonies, the results are shown in FIG. 8.
Comparative example 4
The compound (CORM-Ac) of formula (I-1) is at 106cells/mL of Staphylococcus aureus suspension, after shaking incubation for 30min for fluorescence transition, storing in the dark for 30min, a certain amount of the bacterial suspension was spread on LB agar plates and incubated at 37 ℃, and bacterial activity was evaluated by counting the number of viable bacterial colonies, and the results are shown in FIG. 9.
Comparative example 5
The compound (CORM-Ac) of formula (I-1) is at 106cells/mL E.coli suspension, after shaking incubation for 30min for fluorescence transition, storing in the dark for 30min, a certain amount of bacterial suspension was spread on LB agar plate and incubated at 37 ℃ and bacterial activity was evaluated by counting the number of viable bacterial colonies, and the results are shown in FIG. 9.
Comparative example 6
The compound (CORM-Ac) of formula (I-1) is at 106cells/mL methicillin-resistant Staphylococcus aureus suspension, after shaking incubation for 30min for fluorescence transition, storing in the dark for 30min, spreading a certain amount of the bacterial suspension on LB agar plates, incubating at 37 ℃, and evaluating bacterial activity by counting the number of viable bacterial colonies, the results are shown in FIG. 9.
Comparative example 7
An equal amount of DMSO solvent without the compound of formula (I-1) (CORM-Ac) was added to 106After shaking and incubating staphylococcus aureus suspension for 30min, the suspension was irradiated with a simulated sun lamp for 30min, a certain amount of the bacterial suspension was spread on an LB agar plate and incubated at 37 ℃, and bacterial activity was evaluated by counting the number of viable bacterial colonies, and the results are shown in fig. 10.
Comparative example 8
An equal amount of DMSO solvent without the compound of formula (I-1) (CORM-Ac) was added to 106After shaking and incubating for 30min in the suspension of cells/mL E.coli, the suspension was irradiated for 30min using a simulated sun lamp, a certain amount of the bacterial suspension was spread on LB agar plates and incubated at 37 ℃, and bacterial activity was evaluated by counting the number of viable bacterial colonies, and the results are shown in FIG. 10.
Comparative example 9
An equal amount of DMSO solvent without the compound of formula (I-1) (CORM-Ac) was added to 106cells/mL methicillin-resistant staphylococcus aureus suspension, after incubation for 30min with shaking, the suspension was irradiated with a simulated sun light for 30min, a certain amount of the bacterial suspension was spread on an LB agar plate and incubated at 37 ℃, and bacterial activity was evaluated by counting the number of viable bacterial colonies, the results of which are shown in fig. 10.
Example 5
A solution of the compound of formula (I-1) (CORM-Ac/DMSO solution) was prepared at 106cells/mL Staphylococcus aureus suspension, after shaking incubation for 30min for fluorescence transition, the suspension was irradiated with a simulated sun light for 30min, a certain amount of the bacterial suspension was spread on LB agar plate and incubated at 37 deg.C, and the viable bacterial colony was countedQuantitative evaluation of bactericidal activity, the results are shown in figure 11.
Example 6
A solution of the compound of formula (I-1) (CORM-Ac/DMSO solution) was prepared at 106After shaking and incubating for 30min in the suspension of E.coli, after fluorescence conversion, the suspension was irradiated for 30min using a simulated sun lamp, a certain amount of the bacterial suspension was spread on LB agar plates and incubated at 37 ℃, and bactericidal activity was evaluated by counting the number of viable bacterial colonies, and the results are shown in FIG. 11.
Example 7
A solution of the compound of formula (I-1) (CORM-Ac/DMSO solution) was prepared at 106cells/mL methicillin-resistant staphylococcus aureus suspension, after shaking incubation for 30min for fluorescence transition, the suspension was irradiated with a simulated sun light for 30min, a certain amount of the bacterial suspension was spread on an LB agar plate and incubated at 37 ℃, and bactericidal activity was evaluated by counting the number of viable bacterial colonies, the results of which are shown in fig. 11.
To summarize: the embodiment and the description of the proportion show that the compound with the structure shown in the formula (I) can rapidly change color when in bacterial infection, so that the bacterial infection can be detected; then, the detection system is illuminated, and the result shows that the system has good antibacterial effect, namely, the compound provided by the invention can realize diagnosis and treatment of broad-spectrum bacteria simultaneously.
The above description of the embodiments is only intended to facilitate the understanding of the method of the invention and its core idea. It should be noted that, for those skilled in the art, it is possible to make various improvements and modifications to the present invention without departing from the principle of the present invention, and those improvements and modifications also fall within the scope of the claims of the present invention.

Claims (10)

1. A compound having the structure of formula (I):
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R1is selected fromWherein R is4Is selected from C1-C18Alkyl of (3) or aryl of C6-C50, R5、R6Independently selected from-H and C1-C18Alkyl groups of (a);
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C20, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -C1 or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C20, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
2. A compound of claim 1, wherein R is2Selected from alkyl of-H, C3-C12, aryl of C6-C30, -OH, alkoxy of C3-C12, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
3. A compound of claim 1, wherein R is3Selected from alkyl of-H, C3-C12, aryl of C6-C30, -OH, alkoxy of C3-C12, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
4. A compound of claim 1, wherein R is4Is selected from alkyl of-H, C3-C12 or aryl of C6-C30.
5. A compound of claim 1, wherein R is5、R6Independently selected from-H or C3-C12 alkyl.
6. A process for preparing the compound of claim 1, comprising:
1) mixing the compound with the structure of the formula (II) and the compound with the structure of the formula (III) for reaction to obtain the compound with the structure of the formula (IV),
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -C1 or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br;
2) converting the compound with the structure of the formula (IV) into a compound with the structure of the formula (I);
wherein R is1Is selected fromWherein R is4Is selected from C1-C18Alkyl of (3) or aryl of C6-C50, R5、R6Independently selected from-H and C1-C18Alkyl group of (1).
7. Use of a compound of formula (I) as defined in any one of claims 1 to 5 in the manufacture of a medicament or device for integrating bacterial diagnosis and therapy.
8. A medicament for integrating bacterial diagnosis and treatment, comprising: a compound of formula (I) as claimed in any one of claims 1 to 5 and a pharmaceutically acceptable excipient;
wherein the auxiliary material is one or more of a solvent, an auxiliary agent and a carrier.
9. A photosensitive antibacterial drug has a structure shown in formula (IV),
wherein X is selected from ═ O or ═ S, and Y is selected from-O-or-NH-;
R2selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -C1 or-Br;
R3selected from alkyl of-H, C1-C20, aryl of C6-C50, -OH, alkoxy of C1-C15, -COOH and-NH2、-N(CH3)2、-N(CH2CH3)2-F, -Cl or-Br.
10. The photosensitive antibacterial agent of claim 9, wherein the photosensitive wavelength of the photosensitive antibacterial agent is 300-1100 nm.
CN201910766924.5A 2019-08-19 2019-08-19 Compound and preparation method and application thereof Pending CN110615777A (en)

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