37 results about "Monoamine oxidase" patented technology

The invention provides preparation and application of a novel MAO-B inhibitor containing a tetrahydronaphthalene-1-amine structure, and belongs to the field of medicine. The derivative is a compound as shown in a formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. The compound disclosed by the invention can be used for inhibiting MAO (monoamine oxidase), and particularly can be used for selectively inhibiting MAO-B; the compound can be used for treating Parkinson's disease, Alzheimer's disease, emotional disorder and other diseases, and has a good application prospect.

The invention belongs to the technical field of biological medicine analysis, and particularly relates to a fluorescent probe sequentially responding to gamma-glutamyltranspeptidase and monoamine oxidase and application of the fluorescent probe. The structure of the fluorescent probe is as shown in a formula 1, the fluorescent probe in the formula 1 is constructed by sequentially covalently connecting gamma-glutamyltranspeptidase and specific recognition groups of monoamine oxidase and integrating the gamma-glutamyltranspeptidase and the specific recognition groups of monoamine oxidase into a benzothiazole-xanthene fluorescent parent structure, and the fluorescent probe has near-infrared fluorescence luminescence performance. The probe adopts a double enzyme response activation strategy, and can be activated and generate a fluorescence signal only when gamma-glutamyltranspeptidase and monoamine oxidase exist at the same time, so that the fluorescence probe is high in specificity and has excellent accuracy and specificity in the aspects of pathological imaging, drug safety evaluation and the like.

The invention provides mutant monoamine oxidase and application thereof in synthesis of chiral amine compounds. Specifically, the invention provides monoamine oxidase or a mutant thereof capable of efficiently catalyzing a desymmetric oxidation reaction of 3-azabicyclo [3.3. 0] octane. The monoamine oxidase or the mutant of the monoamine oxidase can be used for efficiently catalyzing 3-azabicyclo [3.3. 0] octane to be subjected to desymmetric oxidation to form (3S, 7R)-3-azabicyclo [3.3. 0] octyl-2-ene, so that the monoamine oxidase or the mutant of the monoamine oxidase can be used for producing chiral amines such as telaprevir intermediates or other chiral amine precursors.

The invention provides a monoamine oxidase mutant, recombinant yarrowia lipolytica and application of the monoamine oxidase mutant and the recombinant yarrowia lipolytica. Monoamine oxidase is subjected to site-directed mutagenesis modification by searching a key catalytic pocket, so that the catalytic efficiency of monoamine oxidase is improved, and biosynthesis of bovine heart alkali is increased; finally, the Phe208Ala mutant is obtained, and the capacity of synthesizing bovine heart alkali by utilizing a genetic engineering strain constructed by the mutant is obviously improved; an MAO-A wild type and a MAO-A mutant are respectively expressed and designed in engineering bacteria, the ability of the mutant for catalyzing dopamine to generate bovine heart alkali in yarrowia lipolytica is compared, and the result shows that the monoamine oxidase mutant can significantly improve the yield of the yarrowia lipolytica bovine heart alkali, the yield is significantly improved by 40.05% compared with an original strain, and the monoamine oxidase mutant has a good application prospect. The method has better performance, can significantly improve the yield of biosynthesized phylline, is more suitable for industrial application in the future development process, and can significantly reduce the production cost and improve the production efficiency.

The present invention provides novel biocatalysts and associated methods of use for the oxidative desymmetrization of fused bicyclic proline analogues to produce APIs and intermediates. The novel biocatalysts of the present disclosure are engineered monoamine oxidase enzymes with improved solubility, thermostability, and activity on fused bicyclic proline compounds, as compared to a reference monoamine oxidase. In particular, the engineered monoamine oxidase enzymes of the present disclosure require reduced enzyme loading for the manufacturing of APIs and intermediates, as compared to a reference monoamine oxidase enzyme.

The present invention provides a series of monoamine oxidases (PMAON) with high catalytic activity and strong chiral selectivity, which are derived from Penicillium, as well as a method for stereoselectively preparing 6,6-dimethyl-3-azabicyclo[3.1.0]hexene compounds using the enzyme. The present invention also provides genes encoding the series of monoamine oxidases, recombinant expression vectors containing the series of genes, recombinant expression transformants and methods for preparing the same.

The present invention relates to a method (100) of synthesizing novel multi¬ effective urea / thiourea compounds which provide simultaneous inhibition of cholinesterase (AChE) and monoamine oxidase (MAO) enzymes known to play roles in Alzheimer's disease (AD); can interact with Ap peptides and / or P amyloid plaque; provide neuroprotective effect by reducing oxidative damage; and to the synthesized compounds and the biological activities they exhibit.

The application discloses a benzothiazole compound containing an acetamide bond, named N-(4-methylbenzothiazole-2-yl)-2-(pyrrolidine-1-yl)acetamide. A preparation method comprises the following steps: first, preparing an N-(4-methylbenzo[d]thiazole-2-yl)-3-chloroacetamide compound; dissolving the N-(4-methylbenzo[d]thiazole-2-yl)-3-chloroacetamide compound and anhydrous potassium carbonate in dichloromethane to obtain a reaction solution; under the condition of an ice water bath and stirring, adding tetrahydropyrrole dropwise into the reaction solution; reacting at room temperature; monitoring the reaction progress by using TLC; after the reaction is completed, quenching the reaction solution by using water; adjusting the pH to neutral; obtaining a solid crude product; and purifying the solid crude product by recrystallization with ethanol to obtain the benzothiazole compound containing the acetamide bond. The compound can effectively inhibit monoamine oxidase and has low cytotoxicity.

The invention discloses a platelet RNA marker combination for detecting non-small cell lung cancer and application of the platelet RNA marker combination, and belongs to the technical field of biological medicine. According to the invention, platelet transcriptome data of a public database NSCLC patient and a healthy control person are compared and analyzed, bioinformatics screening, ROC curve analysis and single center queue verification are carried out, and values of three platelet RNA markers including peroxidase PRDX4, monoamine oxidase MAOB and glutathione transferase GSTM5 in non-small cell lung cancer diagnosis are finally determined. A non-small cell lung cancer diagnosis model based on the platelet RNA marker is successfully constructed, and the vacancy of the platelet RNA marker in the construction of the non-small cell lung cancer diagnosis model is filled.

The invention provides a production method of p-hydroxyacetophenone, which comprises the following steps of: co-expressing phenylalanine amino mutase, L-aspartic acid-beta-decarboxylase, monoamine oxidase and catalase in escherichia coli, converting L-tyrosine into (R)-3-amino-3-(4-hydroxyphenyl) propionic acid through TAM (Transcriptional Amplification Molecule), and converting the (R)-3-amino-3-(4-hydroxyphenyl) propionic acid into (R)-3-amino-3-(4-hydroxyphenyl) propionic acid. According to the method, (R)-3-amino-3-(4-hydroxyphenyl) propionic acid is converted into (R)-4-(1-aminoethyl) phenol through ADC, (R)-4-(1-aminoethyl) phenol is converted into p-hydroxyacetophenone through AOD, and generated hydrogen peroxide is removed through CAT. According to the method, the reaction process is simple, no coenzyme needs to be added, the selected enzyme has the advantages of being high in activity, high in optical specificity and the like, and the p-hydroxyacetophenone is produced through conversion of the recombinant bacterium, so that the method is high in production efficiency, environmentally friendly, low in cost and good in industrial application prospect.

The invention relates to the technical field of traditional Chinese medicine, and discloses acupoint massage essential oil for assisting in controlling smoke and refreshing and a preparation method of the acupoint massage essential oil. Comprising a monarch drug of galangal essential oil, a ministerial drug of lemon essential oil, an adjuvant drug of mint essential oil, an adjuvant drug of coenzyme Q10, an adjuvant drug of limonene, an adjuvant drug of linalool, an adjuvant drug of methyl cinnamate, a conductant drug of jojoba oil and a conductant drug of vanillin. Through synergistic improvement of a formula and a process, effective components of the massage essential oil enter a human body through mutual cooperation of smelling and acupoint massage, the activity of monoamine oxidase is rapidly inhibited, the fragrance is mild, the smell is pleasant, the massage essential oil is convenient to carry and use at any time, and the user experience and the psychological feeling during use are remarkably improved; when the cigarette holder is used, a user can feel pleasant during smoking, untoward effects and pains caused by smoking addiction are relieved, the number of smoking times can be gradually reduced, and the purposes of controlling smoking and quitting smoking are achieved.

The application relates to the technical field of biological medicine, and discloses a novel substituted indigo-coumarin derivative, a preparation method and application thereof. The novel substituted indigo-coumarin derivative has the effects of significantly inhibiting monoamine oxidase-B activity, inhibiting A beta aggregation, resisting oxidation, inhibiting acetylcholinesterase and metal ion chelation, and has therapeutic effects on diseases related to the above mechanisms; in particular, the novel substituted indigo-coumarin derivative has significant therapeutic effects on multiple therapeutic targets of Alzheimer's disease, has low biological toxicity, high safety, has high medical research and market application values. On the other hand, the novel substituted indigo-coumarin derivative is very suitable for large-scale industrial production due to low raw material cost, few reaction steps and simple preparation method.

The invention provides application of monoamine oxidase serving as a catalyst in preparation of quinoline nitrogen heterocyclic compounds. The monoamine oxidase is derived from proteus, pseudomonas, saccharospirillum, marine bacteria RHCI1, photophilic bacteria, vibrio Vibrio sp.JCM 19236 or pseudomonas monteilii. The monoamine oxidase is mild in reaction condition, only recombinant VsMAO whole cells from Vibrio sp.JCM 19236 are used as a biocatalyst, air is used as a molecular oxygen source, pure water is used as a solvent, no toxic reagent is used, the yield of a substrate in a substrate spectrum can reach 99% or above at most, and when VsMAO is used for preparation scale reaction, the VsMAO still shows a good catalytic effect, so that the monoamine oxidase has good application prospects. And an efficient and sustainable way is provided for biological manufacturing of quinoline.

This invention provides a novel MAO-B inhibitor containing a tetrahydronaphthalene-1-amine structure, its preparation and uses, belonging to the pharmaceutical field. The derivative is a compound represented by Formula I, a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. The compound of this invention can be used to inhibit monoamine oxidase (MAO), particularly selectively inhibiting MAO-B; it has promising applications in the treatment of Parkinson's disease, Alzheimer's disease, mood disorders, and other diseases.

The application provides a near-infrared fluorescent probe based on double-enzyme activation of basic dyes, a preparation method and application of the probe, and the Chinese name of the probe compound is 4-(3-(2-amino-4-methylpentanoylamino)propoxy)benzyl 3,7-bis(diethylamino)-10H-phenoxazine-10-carboxylate. The probe can simultaneously detect leucine aminopeptidase (LAP) and monoamine oxidase (MAO), under the action of leucine aminopeptidase, the terminal leucine is hydrolyzed to expose propylamino as a recognition site of MAO, when the probe reacts with MAO, the propylamino is hydrolyzed to release a basic blue 3 fluorophore through a self-immolative group, and red fluorescence is emitted. The compound completes the detection of leucine aminopeptidase and monoamine oxidase through a cascade reaction, the detection signal is obvious, and the color change of the reaction solution can be observed by naked eyes. The application provides an effective visual fluorescent tracking tool for double-enzyme detection in biological detection.

The application discloses pigeon blood antioxidant and anti-aging active peptide and a preparation method and application thereof. The preparation method of the pigeon blood antioxidant and anti-aging active peptide comprises the following steps: adding an anticoagulant to pigeon blood and performing hemolysis pretreatment to dissolve pigeon blood hemoglobin; after the pretreatment, deionized water is added, the blood-water ratio and pH value are adjusted, a protease is added for enzymolysis, the enzyme is inactivated after the enzymolysis is completed, the temperature is cooled to room temperature, the pH value is adjusted to 7.0, and centrifugation is performed to obtain supernatant, and pigeon blood enzymolysis polypeptide is obtained after drying; and the protease is pepsin or trypsin. The pigeon blood active polypeptide prepared by the application can realize the antioxidant and anti-aging effects by adjusting the levels of oxidative stress, monoamine oxidase (MAO), advanced glycation end products (AGEs) and Klotho protein of an aging-regulating gene in brain tissues of D-galactose-induced aging mice.

Provided in the present invention are preparation and use of a novel MAO-B inhibitor containing a tetralin-1-amine structure, which belong to the field of medicines. The derivative is a compound represented by formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. The compound of the present invention can be used for inhibiting monoamine oxidase (MAO), especially selectively inhibiting MAO-B. The compound can be used for treating diseases such as Parkinson's disease, Alzheimer's disease, and emotional disorders, and exhibits good application prospects.

The present invention discloses a strain of Bifidobacterium longum subspecies LF03 and its application in the preparation of antidepressant drugs, belonging to the field of microbial technology. The present invention discloses a strain of Bifidobacterium longum subspecies LF03, and the deposit number is CGMCC No. 23315. Bifidobacterium longum subspecies LF03 can significantly increase the movement distance, mania time, active time of zebrafish in an in vivo insomnia model, and significantly reduce the static time, and significantly inhibit the activity of monoamine oxidase in zebrafish, and has the potential to be used in vivo to prevent or treat depression. The Bifidobacterium longum subspecies LF03 described in the present invention has huge potential application prospects in the preparation of drugs for the treatment and / or prevention of depression.

This invention provides a monoamine oxidase mutant and a recombinant *Yarrowia lipolytica* strain, along with their applications. By identifying key catalytic pockets, site-directed mutagenesis was performed on the monoamine oxidase to improve its catalytic efficiency and increase the biosynthesis of calciferine. The Phe208Ala mutant was ultimately obtained, and the genetically engineered strain constructed using this mutant showed a significantly enhanced ability to synthesize calciferine. The wild-type MAO-A and the designed MAO-A mutant were expressed in the engineered strain, and their ability to catalyze the conversion of dopamine to calciferine in *Yarrowia lipolytica* was compared. The results showed that the monoamine oxidase mutant significantly increased the yield of calciferine in *Yarrowia lipolytica*, with a 40.05% increase compared to the starting strain. This improved performance significantly enhances the biosynthetic yield of calciferine and is more suitable for industrial applications in the future, potentially reducing production costs and increasing production efficiency.

The present invention provides monoamine oxidase and its application in biocatalysis.

The present invention discloses a series of tacrine-selegiline derivatives, their preparation methods, and applications, belonging to the field of pharmaceutical technology. The applicant's experimental results demonstrate that the tacrine-selegiline derivatives provided by the present invention exhibit excellent inhibitory activity against cholinesterase and monoamine oxidase, are promising for the treatment of Alzheimer's disease, and possess excellent potential medicinal value.

The invention belongs to the technical field of biological medicines, and particularly relates to a substituted coumarin-benzoxazole derivative as well as a preparation method and application thereof. The derivative has a structure shown in a formula (I) or (II), R1 is selected from hydrogen, methyl, chlorine and formyloxyethyl, R2 is selected from hydrogen, methyl, trifluoromethyl and a benzene ring, and n is a positive integer ranging from 2 to 5. The preparation is realized through two-step substitution reaction, raw materials are cheap, the process is simple and convenient, and the method is suitable for industrial production. The derivative has remarkable multi-target activity, can inhibit monoamine oxidase-B and beta-amyloid protein aggregation and butyrylcholine esterase at the same time, has a good antioxidant effect, can effectively improve pathological injuries related to neurodegenerative diseases, and is low in biotoxicity and high in safety. The invention can be used for preparing drugs for treating Alzheimer's disease, Parkinson's disease and other diseases, provides a new efficient candidate molecule for the treatment of related diseases, and has important medical research value and market application prospect.

The invention discloses a substituted coumarin-eugenol derivative as well as a preparation method and application thereof. The derivative is prepared by connecting a coumarin mother nucleus and eugenol through a flexible chain by virtue of a two-step nucleophilic substitution reaction. The derivative disclosed by the invention is novel in structure, can simultaneously and effectively inhibit monoamine oxidase-B and acetylcholin esterase and inhibit A beta protein aggregation, has excellent oxidation resistance and metal ion chelation capability, and realizes a multi-target synergistic effect. In-vitro and in-vivo experiments show that the compound has a remarkable improvement effect on a plurality of pathological links such as Alzheimer's disease, and is low in neurotoxicity and high in safety. Meanwhile, the preparation method has the advantages of easily available raw materials and simple steps, is suitable for industrial production, and has a wide application prospect in the aspect of preparing the anti-neurodegenerative disease medicine.

Disclosed are a genetically engineered bacterium catalyzing the production of a quinoline compound, and a use thereof. The genetically engineered bacterium expresses monoamine oxidase and an enzyme capable of catalyzing alcohol oxidation, the enzyme capable of catalyzing alcohol oxidation being selected from alcohol oxidase or alcohol dehydrogenase. It has been unexpectedly discovered that monoamine oxidase coupled to alcohol dehydrogenase or alcohol oxidase can catalyze the preparation of quinoline from amino alcohol substrates, which fills the gap that current biocatalysis methods cannot synthesize amino alcohol substrates into quinoline compounds.

The invention relates to a preparation method and application of a monoamine oxidase treating fluid. The preparation method comprises the following steps: step 1, preparing a buffer solution; step 2, preparing an enzyme inclusion solution; and step 3, sequentially adding 0.25 g / L-0. 5 g / L of flavin adenine dinucleotide and 0.25 g / L-0. 5 g / L of a hydrophilic nonionic surfactant into the continuously stirred enzyme inclusion solution in an environment of 4 + / -1 DEG C, continuously stirring for 30 minutes, filtering, transferring into a dark brown glass bottle, and storing at 2-8 DEG C, thereby obtaining the product. The method disclosed by the invention has the beneficial effects that 1, the problem of too fast enzyme activity loss in the preparation process of the MAO quality control product is solved, and the enzyme activity loss is reduced from original 40% to below 10%; 2, the problem of short preservation period after the MAO quality control product is redissolved is solved, the preservation stability at 2-8 DEG C after the MAO quality control product is redissolved is improved to 7 days from the original 7 hours, and the frozen preservation at-20 DEG C is improved to 30 days from 10 days; and 3, the risk of too high production cost or patent infringement of reagent enterprises caused by MAO raw materials prepared by adopting patented technologies such as gene modification is avoided.

The invention relates to the technical field of molecular detection, in particular to a preparation method of a 5-hydroxytryptamine antibody reagent, and the 5-hydroxytryptamine antibody reagent comprises the following basic components: serum, a 5-hydroxytryptamine receptor diluent, concentrated sulfuric acid, concentrated nitric acid, monoamine oxidase, glyoxylic acid and a developing solution. The basic components for forming the color developing solution are sulfuric acid, nitric acid, glyoxylic acid and ultrapure water, and the mass ratio of the sulfuric acid to the nitric acid to the glyoxylic acid is 30%; 25% of nitric acid; 25% of glyoxylic acid; and 20% of ultrapure water. The reagent has agility, can complete detection in a short time, is suitable for large-scale screening and has convenience, the reagent can observe a result without complex operation of four steps: 1, sampling, 2, centrifuging, 3, mixing of the reagent and a specimen, and 4, standing for 1-15 minutes to obtain the result, the reagent is single, and the operation is simpler and more accurate due to the fact that only a single reagent is provided; and the accuracy of double combination of shaping and quantification is higher.

The invention relates to the field of nanometer material development and nanometer biological medicine and pharmacology, in particular to monoamine oxidation self-polymerization nanoparticles as well as a preparation method and application thereof. The preparation method of the monoamine oxidation self-polymerization nanoparticles comprises the following steps: sequentially adding a tween-80 solution, a 5-HT solution and an alkaline buffer solution into purified water in a water bath at 50-70 DEG C, stirring at 800-1200 rpm, and centrifuging to obtain the monoamine oxidation self-polymerization nanoparticles. The nanoparticles have free radical scavenging capacity, and the scavenging efficiency is in direct proportion to the concentration. After the 5-HT micromolecules are oxidized and self-polymerized to form the nanoparticles, the in-vivo cytotoxicity of the nanoparticles can be remarkably reduced, the biocompatibility is improved, and meanwhile, the nanoparticles have the capabilities of remarkably promoting cell proliferation and migration, inhibiting inflammation-induced cell apoptosis and regulating and controlling the cell cycle. The nanoparticles can also be used as a carrier to be combined with other drugs.

The invention discloses a preparation method of an optically active pydiflumetofen intermediate, which comprises the following specific operation processes: dissolving (+ / -)-O-methyl-N-[1-methyl-2-(2, 4, 6-trichlorophenyl)-ethyl]-hydroxylamine by using an organic solvent, adding into 100mM of PBS (Phosphate Buffer Solution) with pH (Potential of Hydrogen) of 7.5, then adding monoamine oxidase and a chemical reducing agent, continuously introducing oxygen, reacting for 2-3 hours at the temperature of 50-60 DEG C, and finally adding a catalyst, thereby obtaining the optically active pydiflumetofen intermediate. The preparation method comprises the following steps of: stirring and reacting until the reaction is complete, quenching the reaction solution by using a sodium hydroxide solution, filtering the reaction solution by using diatomite to remove the quenched precipitate, extracting the filtrate for three times by using an organic solvent, merging the extract liquor, washing with water, drying by using anhydrous Na2SO4, and concentrating under reduced pressure to obtain the (S)-O-methyl-N-[1-methyl-2-(2, 4, 6-trichlorophenyl)-ethyl]-hydroxylamine. The method has the advantages of being simple in operation process, low in cost, environmentally friendly, capable of saving energy and the like, deracemization of the high-concentration pydiflumetofen intermediate amine can be achieved, the yield is high, and the optical purity of the product is high.

The invention discloses a two-photon fluorescent probe capable of quickly responding to monoamine oxidase and a synthesis method of the two-photon fluorescent probe, and aims to detect the activity of monoamine oxidase in an animal body. According to the method, 2 '-hydroxyacetophenone and p-dimethylaminobenzaldehyde are used as raw materials to synthesize a compound HTC, then the compound HTC reacts with N-Boc-3-aminopropyl bromide, and finally the fluorescent probe HTBA is obtained in a system of trifluoroacetic acid and dichloromethane. According to the invention, the defect of long detection time of a traditional probe is effectively overcome, and after the synthesized fluorescent probe responds to monoamine oxidase, an exposed parent shows a two-photon characteristic, so that not only can interference of background fluorescence signals be weakened, but also high-resolution fluorescence microscopic imaging can be realized, and the penetration depth of tissues is enhanced. Besides, the probe provided by the invention not only can detect the activity of endogenous monoamine oxidase in cells, but also can rapidly detect monoamine oxidase in zebrafish bodies, and the application of the technology provides a more efficient and accurate tool for biomedical research.

The application belongs to the technical field of traditional Chinese medicine, and discloses a kind of smelling and transdermal double-acting smoke control compound acupoint massage essential oil and preparation method thereof, the essential oil takes cinnamon essential oil as monarch drug, chamomile essential oil as ministerial drug, takes peppermint essential oil, limonene, linalool, vanillin, methyl cinnamate as auxiliary drug, and adds vitamin E, rosemary extract, eucalyptol, rose essential oil as auxiliary component.The application solves the core defects of existing essential oil smoke control products through scientific compatibility and process optimization, and each component synergistically inhibits monoamine oxidase activity and regulates dopamine level.Combined with traditional Chinese medicine acupoint massage and nasal smelling double absorption pathway, rapid effect and long-acting smoke control effect are achieved.The application solves the problems of poor user experience, poor stability, slow effect and insufficient targeting of existing smoke control essential oil, has the advantages of good smoke control effect, convenient use, wide applicability, high user acceptance and the like, and is beneficial to improving the success rate of smoking cessation.