239 results about "Enzyme inhibitory" patented technology

The invention discloses a xanthine oxidase inhibitory peptide with uric acid reducing activity and application thereof, and belongs to the technical field of biological medicines.The xanthine oxidase inhibitory peptide is obtained by conducting enzymolysis, separation and purification on processing byproducts such as litopenaeus vannamei heads and shells with xanthine oxidase inhibitory activity. The xanthine oxidase inhibitory peptide is screened by using a molecular docking technology, and the amino acid sequence of the xanthine oxidase inhibitory peptide is Pro-Pro-Val-Pro-Pro-Pro. The xanthine oxidase inhibitory peptide has an XOD (X-Oxidase) half inhibitory concentration of 3.181 + / -0.1786 mM. The invention further proves that the xanthine oxidase inhibitory peptide has a certain improvement effect on hyperuricemia mice, and the xanthine oxidase inhibitory peptide mainly has the effects of reducing the content of serum uric acid, creatinine and urea nitrogen of the hyperuricemia mice, inhibiting the activity of xanthine oxidase (XOD) in serum and liver of the mice, inhibiting synthesis of uric acid and improving kidney injury of the mice, and the xanthine oxidase inhibitory peptide has a certain improvement effect on the hyperuricemia mice through Toxinpred prediction. The xanthine oxidase inhibitory peptide uric acid reducing peptide is free of toxic and side effects and has a wide market application prospect.

The invention discloses bullfrog skin peptide with DPP-IV inhibitory activity and a purification method and application thereof.The molecular weight of the bullfrog skin peptide is 681.40 Da, and the amino acid sequence of the bullfrog skin peptide is shown as SEQ ID NO.1. The bullfrog skin peptide is extracted through an enzymolysis means, then components containing peptide fragments are extracted through a column chromatography purification mode, finally the components are evaluated and screened, and the bullfrog skin peptide with the DPP-IV inhibitory activity is obtained. The purified bullfrog skin peptide with the DPP-IV inhibitory activity is obtained. The bullfrog skin peptide with the DPP-IV inhibitory activity has the advantages of being strong in DPP-IV enzyme inhibitory effect, safe and free of toxic and side effects, has the application potential of hypoglycemic peptides, is short in amino acid sequence and strong in operability, and has good social popularization and application value.

An α-amylase inhibitory peptide. The peptide comprises amino acid sequences of eight adjacent amino acids X1, X2, X3, X4, X5, X6, X7, and X8, wherein each amino acid of the peptide is independently selected from a D-amino acid or an L-amino acid, and at least one of X2, X4, and X6 is W. The peptide has α-amylase inhibitory activity, has the effects of losing weight and lowering blood sugar, and can be used for preparing α-amylase inhibitors, weight-losing drugs, hypoglycemic drugs, or foods, health-care products or drugs for preventing or treating obesity-related diseases.

The invention discloses camel milk polypeptide with xanthine oxidase inhibitory activity and application thereof.The camel milk polypeptide is prepared by taking fresh camel milk as a raw material, conducting low-temperature centrifugation to remove fat, conducting triple enzymolysis through papain, pepsin and trypsin to obtain enzymatic hydrolysate, enabling the enzymatic hydrolysate to pass through an ultrafiltration membrane (the molecular weight cutoff is 10 kDa) to obtain filtrate, and conducting freeze-drying to obtain the camel milk polypeptide. The compound has xanthine oxidase inhibitory activity. The invention also discloses a small molecule polypeptide with xanthine oxidase inhibitory activity. The filtered solution is screened and combined with polypeptides by adopting a xanthine oxidase affinity ultrafiltration method, the activity of the polypeptides is verified through molecular docking and in-vitro enzyme inhibition, four small-molecule polypeptides with xanthine oxidase inhibitory activity are obtained, the sequence of the small-molecule polypeptides is shown as any one of SEQ ID NO.1-4, and the small-molecule polypeptides can be used for preparing drugs with the effect of inhibiting the uric acid level.

The invention relates to the technical field of biology, in particular to a DPP-IV inhibitory peptide extracted from buffalo cheese protein hydrolysate and application of the DPP-IV inhibitory peptide. An active component with the molecular weight smaller than 3 kDa is obtained through alkaline protease enzymolysis, ultrafiltration separation and LC-MS / MS identification, and the DPP-IV enzyme inhibitory activity IC50 value of the active component is 12.6 mg / mL. Four new DPP-IV inhibitory peptide fragments are found, are amino acid sequences in a sequence table SEQ ID NO: 1-4, have good DPP-IV inhibitory activity, and have good application prospects in being developed into functional foods or medicines for regulating blood sugar. In conclusion, the enzymolysis product and the peptide fragment can be prepared into antidiabetic drugs or functional foods, and have the advantages of being natural, safe and efficient. The invention provides a new strategy for high-valued utilization of buffalo milk resources and treatment of type 2 diabetes.

The invention discloses a laccase mutant and application of the laccase mutant in preparation of polyflavone by oxidative conversion of daidzein. According to the invention, laccase Lcc5 of coprinus cinerea is used as a starting enzyme, and through molecular docking, a position structure is analyzed, and mutation is designed. Synthesizing a mutant gene, and constructing a recombinant expression engineering bacterium of the mutant gene. After engineering bacteria containing mutant genes are subjected to induced expression, the Lcc5 mutant Lcc5-T485E is obtained through separation and purification, the specific enzyme activity and ethanol tolerance of the mutant are improved, and the conversion rate of daidzein is increased to about 1.26 times under the same enzyme activity; the antioxidant activity, the enzyme inhibition activity and the antibacterial activity of the obtained conversion product are also remarkably improved. The mutant enzyme has potential application value in oxidative conversion of daidzein and improvement of biological value of daidzein.

The invention discloses a method for preparing various bioactive peptides based on bean dreg fermentation, which comprises polypeptides with alpha-glucosidase inhibitory activity, angiotensin converting enzyme inhibitory activity and antioxidant activity, and belongs to the field of microbial biological fermentation. Bacillus amyloliquefaciens sourced from fermented soybeans is used for fermentation, and a mixed product with alpha-glucosidase inhibitory activity, angiotensin converting enzyme inhibitory activity and antioxidant activity is obtained. The invention also provides a method for purifying the polypeptide with alpha-glucosidase inhibitory activity, angiotensin converting enzyme inhibitory activity and antioxidant activity, which is characterized in that the mixed product is purified by combined column chromatography, the combined column chromatography comprises cation exchange resin LXP-01, macroporous adsorption resin HP20, weak base anion exchange resin D941, silica gel resin and Sephadex LH-20. The invention also discloses seven bioactive peptides with biological activity, the amino acid sequences are CKLLL, APGYSC, FPKYG, FPGPLV, FPRSH, FMAV and SVCC, and the bioactive peptides have good alpha-glucosidase inhibitory activity, angiotensin converting enzyme inhibitory activity and antioxidant activity, and can be used for producing functional foods, health care products, cosmetics and the like for assisting in reducing blood sugar, reducing blood pressure, resisting oxidation and the like.

The invention discloses a small-molecule active peptide with antioxidant and hypoglycemic effects, a composition and application, and belongs to the technical field of biological active peptides. The amino acid sequence of the small molecule active peptide with the antioxidant and blood sugar reducing effects is at least one of FSNAPRL, QFGRLY and SVPGHF. According to the invention, a plurality of micromolecular active peptides with antioxidant and hypoglycemic effects are extracted from walnut meal, the obtained peptide fragment sequence is subjected to molecular docking and chemical synthesis, and the antioxidant activity and hypoglycemic activity of a single peptide fragment and a compound peptide fragment of the synthesized peptide fragment are verified. The active peptide and the compound peptide fragment thereof have good DPPH and ABTS clearance rate and alpha-glucosidase and alpha-amylase inhibition ability, so that the active peptide and the compound peptide fragment thereof have good application prospects in preparation of products with antioxidant and hypoglycemic effects, and a foundation is laid for comprehensive utilization of walnut meal byproducts and promotion of research, development and application of functional active peptides.

The present invention discloses a naphthalimide guanidine derivative, a preparation method thereof and an application thereof. The structural formula of the naphthalimide acyl guanidine compound is shown as formula (I), denoted as CAUZL-C; in formula (I), R is halogen, hydrogen, piperidyl or dimethylamino; n is 1, 2, 3 or 4. The naphthalimide guanidine derivative or a pharmaceutically acceptable salt thereof according to the present invention has good target enzyme inhibitory activity and insecticidal activity.

The present invention provides a compound having a hematopoietic prostaglandin D synthase (H-PGDS) inhibitory activity and being useful for preventing or treating a disease involving the enzyme, and a pharmaceutical composition comprising the compound. Specifically, the present invention provides a compound represented by Formula (I) below or a pharmaceutically acceptable salt thereof:[wherein —X═ represents —CH═ or the like; ═Y— represents ═CH— or the like; R1 and R2 each independently represent a hydrogen atom or the like; R3 represents a hydrogen atom or the like; and Z is a group represented by Formula (II):(wherein the wavy line represents the point of attachment to the nitrogen atom; ring Z1 represents a C6-10 aryl group or the like; m represents 0, 1, or 2; and R4 represents a halogen atom or the like.) or Formula (III):(wherein the wavy line represents the point of attachment to the nitrogen atom; ring Z2 represents a C6-10 aryl group or the like; L represents a single bond or the like; ring Z3 represents a C6-10 aryl group or the like; n represents 0, 1, or 2; and R5 represents a halogen atom or the like.]

According to the preparation method disclosed by the invention, the whole fruit juice of the lonicera caerulea (which retains fruit residues) is fermented by virtue of the plant lactobacillus KLDS1.0391, KLDS1.0320 or KLDS1.0368, so that the xanthine oxidase (XO) inhibition activity is remarkably improved. After fermentation, the XO inhibition rate is increased to 48-50.87% (the content of unfermented juice is 31.21%), the total phenol content is increased by 15-24.3%, and the contents of main XO inhibitors in the lonicera caerulea: cyanidin-3-O-glucoside (IC50 = 115.28 [mu] M), cyanidin-3, 5-diglucoside (IC50 = 116.34 [mu] M), peonidin-3-glucoside (IC50 = 105.34 [mu] M), quercetin (IC50 = 88.75 [mu] M), catechin (IC50 = 110 [mu] M) and caffeoylquinic acid (IC50 = 250.35 [mu] M) are remarkably increased. Wherein the quercetin content is increased by 73.8% at most (KLDS1.0320 strain fermentation is performed for 24 hours), and the XO inhibition rate is increased from 31.21% to 50.87%. Technical support is provided for development of a natural XO inhibitor and a functional fermented beverage, so that a new thought is provided for functional fermented juice with lonicera caerulea as a key component.

The invention belongs to the technical field of biological medicine, and particularly relates to a novel deuterated JAK2 inhibitor or pharmaceutically acceptable salt thereof. Compared with the prior art, the compound or the pharmaceutically acceptable salt thereof provided by the invention has better JAK2 inhibition activity, and the JAK2 inhibition target selectivity of the compound or the pharmaceutically acceptable salt thereof is obviously superior to that of the existing compound, so that the compound or the pharmaceutically acceptable salt thereof has better druggability.

The invention discloses a hexapeptide TE6 with xanthine oxidase inhibitory activity and a preparation method and application thereof, and belongs to the technical field of small molecule peptides. The amino acid sequence of the hexapeptide TE6 is TIATVE, and the hexapeptide TE6 can be prepared through a solid-phase synthesis method and an enzymolysis method. The hexapeptide TE6 is identified from a solieria cavaleriei proteolysis solution and has potential interaction with xanthine oxidase, under the concentration of 0.1 mg / mL, the xanthine oxidase inhibition rate is 44.74%, and compared with goose carnosine (the xanthine oxidase inhibition rate is 36.03%), the xanthine oxidase inhibition rate is remarkably increased (plt; 0.05), which is stronger in xanthine oxidase inhibitory activity, and can be used for preparing a preparation for inhibiting xanthine oxidase activity and relieving hyperuricemia.

Disclosed in the present invention is a phenylthiazolamine-based PI4KIIIβ inhibitor. The inhibitor is a substituted phenylthiazoleamine-based compound represented by general formula V, or a stereoisomer, hydrate, or pharmaceutically acceptable salt thereof. The inhibitor has the characteristic of effectively inhibiting a PI3K / Akt / mTOR signaling pathway of PI4KIII β, and has efficient and excellent PI4KIII β enzyme inhibitory activity, low costs, high efficacy, low toxicity, and a high yield of an intermediate product during synthesis, reducing resource waste, thus facilitating cost reduction; and the inhibitor has a small dosage requirement and significant activity when applied to anti-tumor drugs.

The invention discloses an aryl piperidine compound as well as a preparation method, a pharmaceutical composition and application thereof. The structure of the compound is shown in a formula (I), the compound further comprises an isomer, a prodrug, a stable isotope derivative, pharmaceutically acceptable salt or a mixture of the isomer, the prodrug, the stable isotope derivative and the pharmaceutically acceptable salt, and the compound has a remarkable PRMT5 enzyme inhibition effect and is higher in inhibition activity in the presence of MTA; meanwhile, the inhibitory activity on MTAP-deficient tumor cells is higher than that of a wild type, and selectivity is achieved; the compound has good activity at the molecular level and the cellular level and is wide in application; the preparation method is high in universality and easy for compound structure expansion. # imgabs0 #

The invention relates to a DNMT1-HDAC double-target inhibitor as shown in a formula (I) as well as a preparation method and application thereof, and the DNMT1-HDAC double-target inhibitor not only shows good DNMT1 and HDAC enzyme inhibition activity, but also has remarkable anti-tumor activity on solid tumors and hematoma. As a double-target inhibitor based on DNMT1 and HDACs reported for the first time, the compound has a great prospect in the aspect of cancer treatment; # imgabs0 #

The present invention discloses a class of rutaecarpine derivatives or their pharmaceutically acceptable salts with multi-target anti-tumor activity, and the general structural formula is shown as Formula I or Formula II: #imgabs0# Wherein: R1 is selected from C1-C5 alkoxy, hydroxyl, hydrogen; R2 is selected from hydrogen, halogen; R3 is selected from hydroxyl, #imgabs1# Through enzyme inhibition activity and in vitro anti-tumor activity tests, it was found that the compounds of the present invention have strong inhibitory activities against topoisomerase 1, topoisomerase 2 and c-MYC oncogene, opening up a new way and providing a new strategy for in-depth research and development of anti-tumor drugs with new structural types.

The invention discloses an application of an IMPDH2 inhibitor in preventing or treating inflammation. The limonin compound provided by the invention can be combined with and degrade human inosine-5 '-monophosphate dehydrogenase 2 (IMPDH2), inhibit synthesis of guanine in cells and inhibit activation of an NF-kappa B signal channel, and can be used as an IMPDH2 inhibitor; the IMPDH2 inhibitor also has a relatively good prevention or treatment effect on inflammation. Compared with the existing IMPDH2 inhibitor, the limonin compound provided by the invention can degrade IMPDH2 enzyme, and has better inhibitory activity and stronger activity of inhibiting inflammatory factors.

The invention discloses an (E)-6-(4-carbonyl phenyl) hex-2-ene-1-ketone compound as well as a preparation method and application thereof, the compound can be used as a palmitoyl transferase inhibitor, and the palmitoylation process of substrate protein is further inhibited by inhibiting DHHC protein, so that the inhibition effect on tumor cells is achieved. Embodiments show that the compounds have different degrees of anti-proliferative activity to different cancer cells and different degrees of enzyme inhibitory activity to DHHC proteins, and part of the compounds have better inhibitory activity to cancer cells and DHHC proteins than positive control drugs, and can be further developed into a new generation of antitumor drugs.

The invention belongs to the field of medical chemistry, and particularly discloses an HDAC (histone deacetylase) inhibitor containing a sulfinyl iminobenzamide structure, and the HDAC inhibitor is a compound as shown in a general formula (I) or a pharmaceutically acceptable salt thereof. The invention also discloses a pharmaceutical composition containing the HDAC inhibitor, and the HDAC inhibitor is used for treating cancers and diseases related to neurodegeneration. The HDAC inhibitor prepared by the preparation method disclosed by the invention has surprisingly better HDAC1 enzyme inhibition activity and excellent HDAC1 / 3 selectivity, and has better enzyme inhibition activity on a CoREST compound. # imgabs0 #

The invention discloses eggshell membrane polypeptide with DPP-IV enzyme inhibitory activity and application of the eggshell membrane polypeptide in blood glucose regulation, and belongs to the technical field of biology. The amino acid sequence of the eggshell membrane polypeptide is as shown in SEQ ID NO. 1. According to the invention, a high-activity polypeptide Ala-Pro-Ser-Pro-Trp-Glu is separated and identified from an eggshell membrane, the polypeptide is proved to have certain DPP-IV inhibition ability both in cells and outside cells, the stable DPP-IV inhibition activity is maintained in an in-vitro simulated gastrointestinal fluid environment, and a theoretical basis is provided for research and development of novel diabetes drugs.

The invention discloses spirulina protein-zein composite nanoparticles and a preparation method and application thereof.The preparation method comprises the steps that a zein solution is added into a spirulina protein solution, ethanol in the solution is removed through evaporation, insoluble substances are removed through centrifugation, and spirulina protein-zein composite nanoparticle dispersion liquid is obtained; and freeze-drying to obtain spirulina protein-zein composite nanoparticle powder. The preparation method of the spirulina protein-zein composite nano-particles is simple, low in cost, green and safe, and the obtained nano-particles can be kept stable in a neutral pH environment, have good biocompatibility, can be applied to efficient embedding of bioactive components, and have good application prospects. The light, heat and storage stability of the bioactive components are remarkably improved; and the oxidation resistance, tyrosinase inhibition and in-vitro release performance of the bioactive components are improved.

The present invention discloses an application of an IMPDH2 inhibitor in preventing or treating inflammation. The limonoid compound provided by the present invention can bind to and degrade human inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), inhibit the synthesis of intracellular guanine, inhibit the activation of the NF-κB signaling pathway, and can be used as an IMPDH2 inhibitor; the IMPDH2 inhibitor also has a good preventive or therapeutic effect on inflammation. Compared with existing IMPDH2 inhibitors, the limonoid compound provided by the present invention can degrade the IMPDH2 enzyme, has better inhibitory activity, and has stronger activity in inhibiting inflammatory factors.

The present invention relates to inhibitor compounds and aims to provide an acetohydroxyacid synthase inhibitor, a preparation method therefor, and a use thereof as an herbicide. The structure of the compound is shown in formula (I), and said compound specifically inhibits the activity of acetohydroxyacid synthase or a mutant thereof W574L in plants. The present invention further provides a method for applying said compound as an agrochemical herbicide. The described compound exhibits good enzyme inhibitory activity against wild-type acetohydroxyacid synthase and / or a mutant thereof W574L, and therefore can be used as an agrochemical herbicide for the control of various weeds in the agricultural field. Moreover, the compound can be used as both a pre-emergence and post-emergence herbicide, targeting various field weeds, and is particularly effective in controlling the malignant weed Leptochloa chinensis. The described compound features low dosage, excellent herbicidal activity, broad weed control spectrum, good translocation, wide application window, and safety to rice.

The invention discloses a procyanidine trimer compound, which has a chemical structure as shown in the specification. The hypoglycemic potential of the compound is evaluated through an in-vitro enzyme inhibition experiment, and the result shows that the compound has a remarkable inhibition effect on alpha-amylase, has good water solubility, is derived from natural plant resources, is clear in structure and good in safety, and has a huge application prospect in development of novel natural-source hypoglycemic drugs.

The present invention provides a compound exhibiting coronavirus 3CL protease inhibitory activity or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same. Provided is a compound represented by Formula (I): wherein Ring A is a ring represented by: wherein X is a single bond or the like, R2 is substituted or unsubstituted aromatic carbocyclyl or the like, R3c is substituted or unsubstituted aromatic carbocyclyl or the like, R3 is substituted or unsubstituted aromatic carbocyclyl or the like, R3a is a hydrogen atom or the like, R3b is a hydrogen atom, R8a is substituted or unsubstituted aromatic carbocyclyl or the like, and R8b is a hydrogen atom or the like, R1 is a substituted or unsubstituted aromatic heterocyclyl, m is 0 or the like, R5a is each independently a hydrogen atom or the like, R5b is each independently a hydrogen atom or the like, R6 is cyano or the like, and R7a and R7b are each independently a hydrogen atom or the like, or a pharmaceutically acceptable salt of the compound.

Described herein are novel crystalline forms of the MAGL inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(pyridazin-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate.

The present invention belongs to the technical field of medicines. The present invention relates to an imidazolidinedione HDAC inhibitor, and a preparation method therefor and the use thereof. Provided in the present invention is an imidazolidinedione HDAC inhibitor, which inhibitor is a substituted imidazolidinedione compound as represented by general formula V, or a stereoisomer, a hydrate or a pharmaceutically acceptable salt thereof. The inhibitor has efficient and good HDAC enzyme inhibitory activity, and also has good in-vitro anti-tumor activity. The inhibitor provides a new way for the application of an HDAC inhibitor in tumors / or the treatment of diseases related to uncontrolled histone deacetylase activity.

The present invention discloses a method for preparing milk-derived angiotensin-converting enzyme inhibitory peptides by fermentation with composite strains, which belongs to the fields of microbial technology and fermentation. The ratio of whey protein hydrolysate with a molecular weight below 1000 Da and the angiotensin-converting enzyme inhibition rate in the milk-based fermentation broth are used as evaluation indicators. The composite strain Lactobacillus helveticus ( Lactobacillus helveticus , CICC: 20289), composite strain Pediococcus dilactici ( Pediococcus acidilactici , CICC:20719) were rescreened to obtain strains with excellent whey protein hydrolysis performance and high angiotensin-converting enzyme inhibitory peptide production capacity. The two composite strains obtained from the rescreening were enriched and cultured separately, and then inoculated into skim milk powder culture medium at a specific compound ratio. Through composite fermentation, the angiotensin-converting enzyme inhibitory peptide content in the milk-based fermentation product was increased. The process of this invention is rationally designed and highly operable. It provides a reference for further increasing the content of small molecule functional peptides in fermented dairy products, efficiently preparing milk-derived angiotensin-converting enzyme inhibitory peptides, and improving the nutritional value of dairy products, and has great application prospects.

Provided are an amphotericin B amide derivative and a use thereof. The amphotericin B amide derivative is as shown in formula (I). The compound has good antifungal activity, is effective against various fungi, has good water solubility, is adapted to be developed into an injection dosage form, has excellent metabolic stability in animals (such as mice, rats, dogs, and monkeys), has a long half-life period, can effectively reduce the frequency of administration, has weak inhibition on CYP enzymes, and has a low risk of drug interaction.