27 results about "Evodiamine" patented technology

The invention belongs to the field of microneedle transdermal drug delivery, and particularly relates to an acupoint drug delivery soluble evodia rutaecarpa microneedle as well as a preparation method and application thereof in treatment of oral ulcer. The preparation method comprises the following steps: modifying effective biological components in fructus evodiae to obtain a solid dispersion, and then mixing the solid dispersion with a needle tip matrix to prepare the drug-loaded microneedle. Wherein the effective biological component in the fructus evodiae is evodiamine (EVO) or rutaecarpin (RUT). The medicinal evodia soluble drug-loaded microneedle is prepared, and the medicinal evodia soluble drug-loaded microneedle is attached to the pelma Yongquan acupoint to treat oral ulcer through matching of the medicinal evodia and the acupoint.

A 2,3-fused quinazolinone derivative, its preparation method, and application are disclosed. A 2,3-quinazolinone derivative was synthesized using a simple method with high yield and low production cost. At a concentration of 5 µM and an LPS concentration of 1 µg / mL, compounds 1e and 1f exhibited superior NO release inhibition compared to the anti-inflammatory drugs indomethacin and evodiamine, while compounds 1g and 1q were comparable to indomethacin, and compounds 1w and 1m were comparable to evodiamine. Compounds 1e, 1f, 1g, 1q, and 1m, which exhibited strong NO release inhibition, exhibited less cytotoxicity against RAW264.7 cells than the anti-inflammatory drugs indomethacin and evodiamine. The derivative exhibited significant anti-inflammatory effects and low toxicity. The derivative can be formulated into various dosage forms of anti-inflammatory drugs, possessing high medical value and broad market prospects.

The invention relates to the technical field of medicinal chemistry and pharmacotherapeutics, in particular to a technology and a method for confirming toxic targets of evodiamine (EVO) and accurately evaluating hepatotoxicity of evodiamine. The method comprises the following steps: determining that EVO can be directly combined through biotin labeling, pulldown, mass spectrum combination, small molecule transfection and the like, and up-regulating liver zo-1 protein to cause liver injury, while up-regulating the intestinal tract target is a key mechanism for treating the inflammatory bowel disease by EVO. By comparing the protein levels in the liver-intestine axes of animals in different states, the fact that the down-regulation of the ZO-1 protein level in the liver-intestine axis under the inflammatory bowel disease state can partially antagonize the EVO to the up-regulation of the liver ZO-1 is found, so that the liver toxicity is reduced, and only the therapeutic activity of the EVO is retained. The discovery provides an accurate target spot for understanding an EVO toxicity mechanism, and is beneficial to realizing accurate regulation and control in drug research and development and toxicity prevention in the future; meanwhile, the drug effects and toxic mechanisms of EVO in organisms in different states are compared from the aspect of ZO-1 protein expression in the liver-intestine axis, and direct evidence is provided for the theory of combating poison with poison in toxic traditional Chinese medicine.

The application belongs to the technical field of medicines, and particularly relates to an ester group substituted evodiamine derivative, a preparation method and application, and a structural formula is as follows: The application shows excellent inhibitory activity on HT-29, HTC-116, LOVO, RKO, HGC-27, MGC-803, SGC-7901, Huh7, SK-EP1 and MCF-7 tumor cell lines, and can show good antitumor activity at an animal level.

The application discloses a series of evodiamine derivatives containing pyridine quaternary ammonium salt, a preparation method and antibacterial application thereof. The series of compounds are prepared by introducing a pyridine ring and then connecting with a chloroacetamide fragment based on a natural product evodiamine as a mother structure, so as to prepare a series of evodiamine derivatives containing pyridine quaternary ammonium salt, and the structural general formula is shown in the following formula (1). The series of compounds have strong in-vivo and in-vitro antibacterial activities on Staphylococcus aureus ATCC 29213 and clinically isolated Methicillin-resistant S. aureus (MRSA). The water solubility and antibacterial activity of the application are enhanced through further structure optimization, and the in-vivo and in-vitro toxicity, safe hemolytic activity and low drug resistance are low. Therefore, the evodiamine derivatives containing pyridine quaternary ammonium salt have the potential to be further developed as new antibacterial drugs.

The invention belongs to the technical field of chemical pharmacy, particularly relates to an anti-tumor drug, and particularly relates to an evodiamine derivative, a rutaecarpin derivative and a preparation method and application of the evodiamine derivative and the rutaecarpin derivative. The invention provides an evodiamine derivative and a rutaecarpin derivative with higher in-vivo and in-vitro anti-tumor activity. A new drug fragment is introduced to the N-13 site of a B ring of evodiamine or rutaecarpin for structural modification, and an acylaniline group is adopted to replace a hydrogen atom on an imino group of the B ring of evodiamine / rutaecarpin. A series of evodiamine derivative small molecules and rutaecarpin derivative small molecules which have novel structures and are used for targeted inhibition of DNA topoisomerase are obtained. In-vitro anti-tumor activity research shows that the molecules disclosed by the invention have very strong inhibitory activity on tumor cell strains and can promote apoptosis of tumor cells.

This invention belongs to the field of pharmaceutical application technology, specifically relating to an antifungal evodiamine derivative and its use in the preparation of antifungal substances. The structural formula of the evodiamine derivative is as follows: R1, R2, and R3 are independently H, halogen, or C1-3 alkyl groups; n1 is 1-3; the group is located at the 1, 3, or 4 position of the benzene ring; R4, R5, and R6 are independently C1-3 alkyl groups. The evodiamine derivative has an antifungal effect, especially against Trichophyton rubrum or Trichophyton mentagrophytes, expanding the selection range of antifungal drugs, reducing the possibility of drug-resistant strains, and improving the inhibitory effect on drug-resistant bacteria.

The invention discloses an evodiamine-based NQO1 agonist as well as a preparation method and application thereof, and particularly relates to an evodiamine (EVO) amido bond-connected NQO1 [NAD (P) H: quinone oxidoreductase 1] agonist which shows relatively good non-small cell lung cancer (NSCLC) resistance activity (IC50 is 2.72 M) through a cytotoxicity experiment. The compound provided by the invention promotes A549 cell apoptosis, blocks a cell cycle to a G2 / M period, causes active oxygen outbreak, and down-regulates the expression of Keap1 and up-regulates the expressions of Nrf2, NQO1 and HO-1 after acting in A549 cells for 24 hours. The results show that the compound can improve the cell antioxidant ability by adjusting the Keap1 / Nrf2 / NQO1 antioxidant pathway. In-vivo anti-tumor experiments show that the compound can inhibit proliferation of tumor tissues (TGI = 39.13%). In a word, the research result shows that the compound has a strong excitation effect on an NQO1 signal channel, and a potential opportunity is provided for improving treatment of non-small cell lung cancer.

The application discloses a class of evodiamine derivatives targeting insect ryanodine receptors and preparation and application thereof. The compound of the application has a structural formula as shown in I, wherein R, R 1 , R 2 are defined in claim 1. The compound of the general formula I of the application has medium to excellent insecticidal activity on pests of Lepidoptera such as oriental armyworm and diamondback moth, and research on the insecticidal mechanism finds that it is a class of insect ryanodine receptor activators. The application synthesizes a class of insecticides targeting insect ryanodine receptors, which can be used alternatively with existing insecticides to avoid or delay the generation of resistance, has conventional preparation conditions, simple subsequent treatment and is easy to realize industrialization, and is an insecticide with wide application prospect.

The invention belongs to the field of biological pharmacy, and particularly discloses application of evodiamine in inhibition of migration and invasion of gallbladder cancer cells and metastatic tumor growth. Aiming at the problems of poor drug targeting, high toxicity, easy drug resistance and the like in gallbladder cancer hepatic metastasis treatment, the invention provides various application forms of evodiamine: 1) an evodiamine single-drug sustained release preparation (PLGA or chitosan carrier) realizes long-acting sustained release through local intervention or intratumor injection; 2) the evodiamine liposome preparation (the ratio of DPPC to cholesterol is 3: 1, and the particle size is 80-150nm) can improve the enrichment rate of hepatic metastatic focus to 5.8% or above; (3) the evodiamine and chemotherapeutic drugs (oxaliplatin, 5-FU and the like) are combined to form a composition, and the synergy index is Cilt; 0.8, the toxicity of the system is obviously reduced; animal experiments show that the liver metastasis inhibition rate reaches 82.7% and the weight loss rate is only 10.5% when the liposome (3 mg / kg of evodiamine and 6 mg / kg of oxaliplatin) is combined, and a high-efficiency and low-toxicity solution is provided for gallbladder carcinoma metastasis.

The invention discloses a synthesis method of a 10-aryl evodiamine derivative in the field of new drug design and synthesis, the 10-aryl evodiamine derivative has a structural formula shown as a formula 4, and R is selected from H, alkyl, alkoxy or halogen atoms. The synthesis route is shown in the specification. Comprising the following steps: (1) taking 10-hydroxyevodiamine (1) as a raw material, and reacting the 10-hydroxyevodiamine (1) with trifluoromethanesulfonic anhydride (Tf2O) under proper conditions to obtain 10-trifluoromethanesulfonyloxy evodiamine 2; (2) reacting the compound 2 with an arylboronic acid reagent 3 under proper conditions to obtain a 10-aryl evodiamine derivative 4; wherein R of the arylboronic acid reagent 3 in the step (2) is selected from H, alkyl, alkoxy or halogen atoms. The 10-aryl evodiamine derivative 4 synthesized by the invention shows good anti-cancer activity on liver cancer cells and neuroblastoma cells, and can be applied to preparation of corresponding anti-tumor drugs.

The invention discloses a nano-drug for co-delivery of evodiamine and Ppa as well as a preparation method and application of the nano-drug, and a pharmaceutical composition is a TPGS (at) EVO / Ppa nano-drug and comprises evodiamine (EVO), pyropheophorbide-A (Ppa) and a drug carrier vitamin E polyethylene glycol succinate (TPGS). The nano-drug has a synergistic anti-tumor effect, further enhances the immunotherapy effect, has a remarkable killing effect on tumor cells under laser irradiation, and can effectively inhibit tumor growth.

The present application relates to a kind of methods based on transcriptome sequencing, machine learning and molecular docking analysis of evodiamine treatment vestibular schwannoma (VS), the present application is analyzed by integrating transcriptome sequencing technology and GEO database, combined with machine learning algorithm, molecular docking and molecular dynamics simulation method, the potential key target and signal pathway of evodiamine treatment VS are systematically analyzed, provide technical support for the mechanism research of evodiamine, and provide reference basis for future individualized treatment strategy of VS.

The invention belongs to the field of new drug design and synthesis, and relates to a synthesis method of a 10-arylamino evodiamine derivative, the 10-arylamino evodiamine derivative is shown as a formula 4, and R is selected from H, alkyl, alkoxy or fused aryl. The synthetic route comprises the following steps: (1) taking 10-hydroxyevodiamine (1) as a raw material, and reacting with trifluoromethanesulfonic anhydride (Tf2O) under proper conditions to obtain 10-trifluoromethanesulfonyloxy evodiamine 2; (2) reacting the compound 2 with an arylamine reagent 3 under proper conditions to obtain a 10-arylamine evodiamine derivative 4; wherein R of the arylamine reagent 3 in the step (2) is selected from H, alkyl, alkoxy or fused aryl. The 10-arylamino evodiamine derivative 4 synthesized by the invention shows good anti-cancer activity on liver cancer cells and neuroblastoma cells, and can be applied to preparation of corresponding anti-tumor drugs.

The rutaecarpin and the derivative thereof are synthesized by using a hydrogen borrowing reaction strategy. In an experiment, ethylene glycol is used as a solvent and an alkylating reagent, and the ethylene glycol and a substrate are subjected to a heating reaction in the presence of an iridium-based catalyst under an alkaline condition to prepare a target product. In the reaction process, two hydroxyl groups in the ethylene glycol are respectively and successively converted into formyl groups, and then a nucleophilic addition reaction of aldehyde is carried out; and the alkylation reaction is completed through the steps of dehydration, reduction and the like. In the whole reaction process, hydrogen and other reducing agents do not need to be additionally added, and only water serves as a byproduct. Therefore, from the perspective of synthetic chemistry and environmental protection, the hydrogen borrowing reaction method has the characteristics of high efficiency and greenness, and has a wide application prospect.

The present invention belongs to the technical field of chemical pharmaceuticals, and particularly relates to anti-tumor drugs. Specifically, it relates to an evodiamine derivative, a rutaecarpine derivative, and their preparation methods and applications. The present invention provides an evodiamine derivative and a rutaecarpine derivative with higher anti-tumor activity in vitro and in vivo. By introducing a new drug fragment at the N-13 position of the B ring of evodiamine or rutaecarpine for structural modification, and using an acyl aniline group to replace the hydrogen atom on the imino group of the B ring of evodiamine / rutaecarpine, a series of novel small molecule evodiamine derivatives and small molecule rutaecarpine derivatives that target and inhibit DNA topoisomerase are obtained. The study of anti-tumor activity in vitro shows that this type of molecule described in the present invention has strong inhibitory activity against tumor cell lines and can promote the apoptosis of tumor cells.

The invention discloses a method for analyzing a toxic target of evodiamine based on a network toxicology system. The method comprises the following steps: SA, locking the toxic target; wherein the step SA comprises the following steps: step SA1, obtaining a potential toxic target spot of evodiamine of each toxic object in at least two toxic objects; sA2, locking a core toxic target spot of each toxic object; step SA3, locking a comprehensive core toxicity target spot; the comprehensive core toxicity target spot is a core toxicity target spot simultaneously existing in all toxic objects; wherein the sequence of the step SA1 and the step SA2 is not different. Based on the steps, the method not only locks the core toxicity target spot of each toxicity redemption, but also further locks the core toxicity target spots existing in all toxic objects at the same time, and can help to guide subsequent research to preferentially and sequentially determine research key points, improve research efficiency and save manpower and material resources.

This invention belongs to the field of pharmaceutical technology, specifically relating to a water-soluble evodiamine derivative and its application, with the following structural formula: wherein X is a C1-6 alkylene group or X together with R forms R1 and R2 independently selected from hydroxyl or C1-20 alkoxy groups; R is a hydroxyl group with or without alkylene group, a carboxyl group with or without alkylene group, a C1-20 oxane group, an amino group, a substituted amino group with or without alkylene group, or a heterocyclic amino group with or without alkylene group. This invention can improve its water solubility and antitumor effect.

The invention discloses 9-phenyl-10-alkoxy evodiamine quinazolinone with a structural formula as shown in a formula 3, wherein R is selected from alkyl or substituted alkyl. The designed and synthesized 9-phenyl-10-alkoxy evodiamine quinazolinone derivative as shown in 3 is prepared by the following steps: (1) taking 10-hydroxy evodiamine (A) as a raw material, and reacting with an alkylation reagent (RX) in the presence of a proper alkali catalyst under proper conditions to obtain 10-alkoxy evodiamine 1, 2, 3-triazole; (2) reacting the compound 1 with a bromination reagent under proper conditions to obtain 9-bromo-10-alkoxy evodiamine 2; and (3) reacting the compound 2 with an arylboronic acid reagent under proper conditions to obtain the 9-phenyl-10-alkoxy evodiamine quinazolinone derivative 3. The 9-phenyl-10-alkoxy evodiamine quinazolinone derivative synthesized by the invention shows good anti-cancer activity on liver cancer cells and neuroblastoma cells in vitro, and can be used for preparing corresponding anti-cancer drugs.

The invention relates to an evodiamine analogue as well as a preparation method and application thereof, and belongs to the field of organic chemistry. A target compound is synthesized through an intramolecular hydrogen borrowing reaction by taking a 2-indolyl quinazolinone derivative as a substrate and using a nickel-based catalyst. The method is simple in route, high in yield and low in production cost. When the concentration is 1 [mu] M / L, the inhibition effects of the target compounds 1k and 1o on the proliferation of in-vitro human colon cancer cells HCT-116 are superior to that of the medicine evodiamine, and the inhibition effects of the target compounds 1k and 1o on the proliferation of the in-vitro human colon cancer cells HCT-116 are equivalent to that of the medicine In addition, the inhibition effects of the compounds 1d, 1k and 1o on proliferation of in-vitro human bladder cancer cells T24 are better than those of evodiamine; it shows that part of target compounds have potential medicinal values.

The invention relates to the technical field of evodia rutaecarpa, in particular to an evodiamine toxicity-reducing and effect-preserving compatible composition. The preparation method comprises the following steps: S1, carrying out compatibility on evodiamine and rutaecarpin to obtain a compatible medicament; and S2, applying the compatible medicament obtained in the step S1 to zebra fish, and judging whether the medicament has an attenuation effect or not. According to the compatibility of evodiamine and rutaecarpin, it is proved that when the evodiamine and rutaecarpin are used in experiments in zebra fish, it is proved that the evodiamine and rutaecarpin have the toxicity reducing effect in application according to data such as phenotypic experiments, pathological section staining and biochemical index detection, and through tests on C57 mice, the evodiamine and rutaecarpin have the toxicity reducing effect. The traditional Chinese medicine composition is proved to be capable of effectively improving intestinal inflammation of mice, repairing intestinal barriers and realizing the effects of reducing toxicity and keeping effect.

The invention belongs to the technical field of medicines, discloses an oxa-evodiamine compound and a pharmaceutical application thereof, and particularly provides the oxa-evodiamine compound shown as a formula (I), and physiologically acceptable salts and pharmaceutical compositions thereof. The compounds can effectively inhibit proliferation of pulmonary artery smooth muscle cells caused by PDGF-BB, and can be used for preventing or treating pulmonary arterial hypertension. # imgabs0 #

The application belongs to the technical field of medicine, and discloses evodiamine compounds and pharmaceutical uses thereof, and provides evodiamine compounds shown in formula (I), and their physiologically acceptable salts and pharmaceutical compositions. The compounds have good inhibitory activity on HDAC6, and can be used for preventing or treating HDAC6 related diseases.

The invention discloses an evodiamine conjugate or a pharmaceutical salt thereof. The structural general formula of the evodiamine conjugate or the pharmaceutical salt thereof is selected from one of the following structures, according to the invention, a compound 1a or a compound 1b with an extremely strong in-vitro inhibition effect on tumor cell growth is used as a pharmacophore to be fused with an Hsp90 inhibitor, and the Hsp90 inhibitor, namely the evodiamine conjugate, is designed and synthesized. According to the evodiamine conjugate disclosed by the invention, an Hsp90 inhibitor in the structure is partially combined with eHsp90 secreted into a microenvironment by tumor cells in a targeting manner, and the tumor targeting property of the evodiamine conjugate is remarkably improved compared with that of a compound 1a and a compound 1b under the cell endocytosis mediated by the eHsp90, so that a new strategy is expected to be provided for improving the tumor treatment effect of a natural product and a derivative thereof.

The invention discloses a preparation method of dehydroevodiamine and a dehydroevodiamine salt, and relates to the technical field of organic synthesis.The preparation method comprises the steps that evodiamine is dissolved in an organic solvent, a dehydrogenation reaction is conducted under the illumination condition, and dehydroevodiamine is obtained; evodiamine is dissolved in an organic solvent and reacts with acid under the action of a catalyst, and the dehydroevodiamine salt is obtained. According to the method, the problems that the process is tedious, the period is long, the production efficiency is low, the environmental protection property is poor and the like when the dehydroevodiamine is extracted, separated and prepared from plants are solved; meanwhile, the defect that demethylation side reaction easily occurs in the synthesis reaction process of the dehydroevodiamine is overcome, and efficient synthesis of the dehydroevodiamine and the dehydroevodiamine salt is achieved.

The invention discloses a construction method of a specific chromatogram of a Shuangjin gastrointestinal capsule, and belongs to the technical field of quality control and management of compound traditional Chinese medicine preparations. The preparation method comprises the following steps: taking different batches of Shuangjin gastrointestinal capsules as test samples, and taking chlorogenic acid, hesperidin, daidzein, nardosinone, caffeic acid, linarin, dehydrocostus lactone, rutaecarpin, limonin, nobiletin, tangeretin, epiberberine, genistin, daidzein, succinic acid and uridine as reference substances; high performance liquid chromatography and mass spectrometry are combined for detection, and the specific chromatogram of the double-jin gastrointestinal capsule is obtained. The method is simple and easy to implement, high in precision, good in reproducibility, accurate and reliable, at least 16 components are confirmed at a time under the same chromatographic condition, time and cost are saved, and the detection efficiency is improved; the method can accurately, clearly, objectively, quickly and comprehensively monitor the quality of a plurality of characteristic components of the Shuangjin stomach and intestine capsule at the same time, and has important effects and values for controlling the quality of the Shuangjin stomach and intestine capsule and ensuring the clinical curative effect.

The invention belongs to the technical field of biological medicines, and discloses application of a small-molecule Fibrillin-1 inhibitor in preparation of a medicine for treating chronic kidney diseases. According to the application of the evodiamine or the pharmaceutically acceptable salt of the evodiamine in inhibiting the activity of the fibrillar protein-1 or preparing the fibrillar protein-1 inhibitor, the Evodiamine is subjected to a molecular interaction experiment and a cell phenotype experiment, and results show that the Evodiamine can be used as a small-molecule inhibitor of FBN1 and can effectively inhibit the phenotype of mesangial cell fibrosis induced by the FBN1. Furthermore, Evodiamine can significantly inhibit podocyte damage, mesangial cell activation and glomerular sclerosis progress, and can be used for effectively inhibiting CKD progress to achieve the purpose of treatment.