282 results about "Lead compound" patented technology

The invention discloses a hexapeptide with a hypoglycemic effect as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The amino acid sequence of the hexapeptide is Ile-Trp-Asp-Pro-His-Phe, and the amino acid sequence of the hexapeptide is as shown in the specification. The novel hexapeptide IWDPHF with prominent DPP-IV inhibition ability is successfully identified from mulberry leaf proteolysis products through liquid chromatography-mass spectrometry and a virtual screening method, the hexapeptide IWDPHF shows the blood glucose reducing effect superior to that of part of known peptides in an in-vitro enzyme activity inhibition experiment and a zebra fish hyperglycemia model, and no obvious side effect exists; the compound has a good potential of being developed into a hypoglycemic functional product or a drug lead compound. The invention further provides the mulberry leaf peptide with the peptide fragment IWDPHF, and the mulberry leaf peptide can be applied to preparation of drugs or food for reducing blood sugar. The invention provides a new scheme and theoretical basis for treatment of diabetes, and has good market prospect and application potential.

The invention discloses a novel benzofuran component in eupatorium chinense and application of the benzofuran component in anti-inflammatory activity. The obtained compound is separated from an eupatorium chinense extract. The eupatorium chinense root extract is separated by using an extraction method, macroporous adsorption resin impurity removal, Sephadex LH-20 gel column chromatography, high performance liquid chromatography and other methods. According to the present invention, all the separated compounds and the analogues thereof have good inhibition activity on target cyclooxygenase-2 of inflammation-related diseases, and have good inhibition activity on COX-2 enzyme, and the molecular docking experiment results show that the compounds and the target proteins have good binding energy. Therefore, the compound can be used for preparing drugs for treating inflammatory related diseases, or anti-inflammatory and analgesic drugs, or tumor drugs by inhibiting COX-2 enzyme, such as drugs for rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, Alzheimer's disease and the like, and related natural lead compounds are provided.

The invention discloses a multi-target joint optimized antibiotic molecule design system and method applied to the field of biological medicine, and the method comprises the steps: obtaining FabI enzyme and AcrAB-TolC efflux pump structure data, extracting double-target space and physicochemical characteristics, and constructing a joint pharmacophore model containing a FabI inhibition domain and an efflux pump blocking domain; screening candidate molecules meeting a double-domain space matching threshold, screening high-affinity double-target molecules through conformation sampling and free energy calculation, and forming a lead compound library through multi-layer filtration of metabolic stability, membrane penetrability, quantum chemical properties and synthesis feasibility; carrying out electron effect, chain length or heteroatom fine tuning on dominant molecules through in-vitro bacteriostasis and efflux inhibition experiment feedback, and carrying out iterative optimization until MIClt is met; 2 [mu] g / mL and the efflux inhibition rate is gt; according to the present invention, the antibacterial effect and the drug resistance inhibition ability are significantly improved, the molecular synthesizability and the biological safety are ensured, and the engineering design new path is provided for the Gram-negative bacterium drug resistance crisis.

The application discloses a kind of miraculin compounds and its extraction method and application, belong to the field of traditional Chinese medicine extraction, specifically related to a kind of miraculin compounds as shown in general formula (I) and (II) isolated from Rhododendron dauricum and the extraction method of the compound, and the compound or the isomer of the compound, or the inhibitory effect of the compound on inflammation in pharmaceutically acceptable salt or pharmaceutical composition comprising the compound can be used for preparing anti-inflammatory drugs.The application further enriches the structural diversity of active substances of Rhododendron dauricum, which lays a foundation for subsequent related biological activity tests of monomeric compounds, provides active lead compounds for new drug development, and also provides a theoretical basis for in-depth research and development of Rhododendron dauricum medicinal materials.

This invention discloses a benzofuran compound and its application in lowering uric acid activity. Compounds 1-3 were isolated from the fermentation products of the endophytic fungus *Septoriella phragmitis*, with compound 1 being a novel compound. The fermentation products were purified using mixed solvent extraction, normal silica gel column chromatography, and high-performance liquid chromatography to obtain compounds 1-3. The inhibitory activity of compounds 1-3 on xanthine oxidase, a target related to gout symptoms, was tested. Experimental results showed that the novel compound 1 exhibited good inhibitory activity against xanthine oxidase. Molecular docking experiments also demonstrated that compound 1 had a good binding energy to the target protein. Therefore, compound 1 can be used to prepare a natural lead compound for delaying or treating diseases caused by xanthine oxidase, providing a potential therapeutic agent for hyperuricemia and gout.

The present invention discloses a series of phenylurea derivative compounds, specifically relating to the compounds as free base, or isomer, or solvate, or pharmaceutically acceptable salt forms; methods of preparing medicaments; compounds composition, and therapeutic uses thereof. The present invention has developed a series of structurally novel compounds based on histamine H3 receptor ligands, and a series of relevant biological tests have been performed on the compounds. The results of the tests all indicate that the compounds have significant H3 receptor antagonistic activity and can be used as lead compounds for the prevention or treatment of H3 receptor-related diseases.

The invention relates to the technical field of chemical synthesis, and particularly discloses an indolone compound and a preparation method thereof. The structure of the indolone compound is shown as a formula (I). The one-step substitution reaction-based indolone compound preparation method provided by the invention has the outstanding advantages of mild reaction conditions, simple operation steps, high product yield and the like, and effectively overcomes the common problems of tedious steps, harsh conditions, poor selectivity and the like in the existing synthesis route. Establishment of an efficient synthesis route provides a reliable way for rapid and large-scale preparation of indolone derivatives with novel structures. The series of novel indolone compounds with potential excellent biological activity provide a new opportunity for discovery of innovative drug lead compounds and development of novel functional materials, and have important research value and wide application prospects. Formula (I)

The application belongs to the field of genetic engineering and biosynthesis, and particularly relates to biosynthesis of a class of diterpenoids. The application provides genes having a key role in the formation of a 5-8-5 tricyclic mother nucleus and a five-membered heterocyclic ring in biosynthesis of the class of diterpenoids, which are respectively named as PrcA and PrcB and polypeptides encoded by the genes, expression of PrcA and PrcB is carried out through a heterologous expression system of Aspergillus oryzae, and five diterpenoids with novel structures and anti-metabolic related fatty liver disease activity are obtained. The application provides application of the polypeptides in biosynthesis of the class of diterpenoids, and enriches a diterpenoid library, thereby providing lead compound resources for discovering new anti-metabolic related fatty liver disease medicinal raw materials.

This invention belongs to the field of organic synthetic chemistry technology, specifically relating to a selenium-based indoloquinazoline derivative, its preparation method, and its application, comprising: in an organic solvent, using aromatic amine compounds, malononitrile, and diselenoether as raw materials, in the presence of a palladium catalyst and an organic base, at 90°C... o The reaction was carried out under C conditions with stirring to obtain a selenyl indoline quinazoline derivative. This method features mild reaction conditions, simple operation, high yield, and good functional group compatibility, conforming to the principles of green chemistry. Furthermore, the selenyl indoline quinazoline derivative provided by this invention exhibits good inhibitory activity against Plasmodium, providing a drug lead compound for the development of novel antimalarial drugs and holding significant importance for the prevention and / or treatment of malaria.

This invention relates to the use of a natural terpene compound in pharmaceuticals, said natural terpene compound having the structure shown in formula (I), and having the function of preparing a compound for the prevention or treatment of hypoxia-inducible factor-1. α Use in medicines for diseases associated with abnormally elevated activity. This invention has discovered that the compound possesses hypoxia-inducible factor-1. α It exhibits inhibitory activity, effectively suppressing macrophage inflammatory responses and hepatocyte damage. It also demonstrates significant protective function against lipopolysaccharide / galactosamine-induced acute liver injury in mice, and can be used as a lead compound for the preparation of new drugs or drugs for the prevention and treatment of acute liver injury.

The application provides a dual-target piperine compound used as an alpha-glucosidase inhibitor and an aldose reductase inhibitor, the compound has a general structure of piperine, a series of structural modifications are carried out based on piperine, and finally a series of dual-target piperine compounds are synthesized. The dual-target piperine compound provided by the application can simultaneously inhibit the activities of alpha-glucosidase and aldose reductase, has the function of dual targets, can be used as a new alpha-glucosidase inhibitor and aldose reductase inhibitor, and is used as an anti-diabetic drug or for preparing an anti-diabetic drug.

The present application relates to the technical field of biological medicine, in particular to a curcumin analogue, a synthetic method and application thereof. The present application takes curcumin as a lead compound, introduces cyclopropylmethyl, n-butyl and isobutyl in acetylacetone, introduces 4-acetylamino, 3,4-dimethoxy, 2-fluoro and 3-trifluoromethyl on a benzene ring, and designs and synthesizes a series of curcumin analogues. In vitro cytotoxicity experiments show that the killing effect of the newly synthesized curcumin analogue on prostate cancer cells is stronger than that of dimethyl curcumin, and the androgen receptor inhibition effect is also stronger than that of dimethyl curcumin.

Phthalide lactones, as an important class of benzopentolactone skeleton, are widely distributed in natural products, medicinal plants and bioactive molecules, and have significant pharmacological activities and synthetic application potential. This kind of structure not only shows various biological activities such as antibacterial, anti-inflammatory, antitumor, antioxidant, but also is an indispensable core structural unit in many drug molecules and lead compounds. At the same time, cyano is a very valuable functional group in the field of organic synthesis and medicinal chemistry, with strong electron-withdrawing properties, strong structural stability and other advantages, which can effectively improve the electronic distribution, lipid solubility and drug performance of the molecule. In view of the important significance of phthalide lactones and cyano in organic synthesis and drug research and development, the present invention develops a synthetic method for efficiently constructing cyano-containing alkyl chain substituted phthalide lactone compounds. It has important value in medicinal chemistry and organic synthesis.

The invention discloses a ferulic acid derivative and a preparation method and application thereof.The ferulic acid derivative is a compound shown in the formula (I) or pharmaceutically acceptable salt of the compound, and the compound is a natural compound extracted from rubus corchorifolius stems, has anti-inflammatory activity and anti-tumor activity and has the potential of being developed into anti-inflammatory or anti-tumor drugs. Or as a lead compound.

The invention relates to the technical field of traditional Chinese medicine extraction and separation, in particular to two alkaloid compounds in portulaca oleracea and an extraction and separation method and application thereof. The molecular formulas of the two kinds of alkaloid compounds are both C27H33NO15, and the two kinds of alkaloid compounds are respectively named as oleraclamie K and oleraclamie L. The invention further discloses a preparation method of the oleraclamie. According to the method, water extraction, ODS column chromatography, Sephadex LH-20, a high performance liquid chromatograph and the like are adopted for separation, purification and preparation, the compounds oleraclamie K and oleraclamie L are successfully extracted and separated out, the method is simple, convenient and rapid, the extraction and separation process mainly adopts a water extraction process, the method is environmentally friendly, the purity of the compounds separated through the method is high and larger than 90%, and the method is suitable for industrial production. In addition, researches show that the two compounds have anti-inflammatory effects, so that the alkaloid compound and the salt and the derivative thereof can be used as synthesis primers of other compounds and raw materials for new drug development and pharmacological activity research, and can also be used for preparing anti-inflammatory drugs.

The invention discloses a tetrahydrofuran lignan compound as well as a preparation method and application thereof, the tetrahydrofuran lignan compound is a compound shown as a formula (I) or pharmaceutically acceptable salt thereof, the compound is a natural compound extracted from rubus corchorifolius stems, has anti-inflammatory activity and anti-tumor activity, and can be used for preparing a medicine for treating tumors. The compound has the potential of being developed into anti-inflammatory or anti-tumor drugs and can be used as a lead compound.

This invention discloses a class of pentacyclic triterpenoid derivatives with diverse B-ring modifications, their preparation methods, and applications. This invention utilizes a chemical enzymatic method to expand the chemical space of the B-ring in pentacyclic triterpenoids, obtaining a series of pentacyclic triterpenoid derivatives with diverse B-ring modifications. Pharmacological activity screening of these pentacyclic triterpenoid derivatives revealed their good tumor-suppressive activity, providing a promising application prospect for the prevention and treatment of tumors. This invention achieves the efficient synthesis of pentacyclic triterpenoid derivatives with diverse B-ring modifications, structures that are difficult to obtain using traditional chemical methods. Systematic antiproliferative activity screening identified candidate molecules with broad-spectrum and highly efficient inhibitory effects against various human tumor cell lines. These molecules show good drug development potential, providing novel lead compounds for the innovative development of anticancer drugs.

The invention provides an application of 2-indolecarboxylic acid in preparation of a tumor targeted therapy drug. Through computer-aided drug design and molecular docking optimization, 2-indolecarboxylic acid shows high binding energy to an HER2 kinase structural domain. In HER2 positive NCI-N87 gastric cancer cells, the 2-indolecarboxylic acid significantly inhibits cell proliferation and induces G0 / G1 phase arrest and apoptosis. The mechanism research shows that the 2-indoleformic acid can play a role by regulating and controlling the HER2 / Akt / beta-catenin pathway (Western blot verification). In an NCI-N87 cell tumor-bearing nude mouse model, 2-indolecarboxylic acid (15 mg / kg) significantly inhibits tumor growth, and does not cause obvious weight loss or organ toxicity. Immunohistochemical analysis shows that the positive rate of a tumor tissue proliferation marker Ki-67 in a treatment group is remarkably reduced, and apoptosis detection shows that the proportion of TUNEL positive cells is remarkably increased, which indicates that 2-indolecarboxylic acid inhibits tumor cell proliferation and promotes apoptosis at the same time. The invention provides a lead compound with clinical transformation potential for HER2 targeted therapy.

The invention belongs to the technical field of medicines, and particularly relates to a phenanthroindolizidine alkaloid compound and application thereof. The invention discloses two kinds of phenanthroindolizidine alkaloid compounds, namely (-)-(R)-13a alpha-secoxanthin and (-)-(R)-13a alpha-6-O-desmylanthin, which are derived from a traditional Chinese medicine cynanchum atratum, and discloses the obvious anti-neuritis activity of the phenanthroindolizidine alkaloid compounds for inhibiting the generation of nitric oxide. Animal experiments prove that by intraperitoneal injection of the (-)-(R)-13a alpha-secoxanthin and the (-)-13a alpha-6-O-desmylanthin, the autonomous movement ability of a depression mouse is remarkably improved, the exploration behavior of the mouse is recovered, the anxiety symptom of the mouse is relieved, and the despair behavior of the mouse is relieved. The invention provides a new lead compound for research and development of new antidepressant drugs.

The invention relates to a sterol compound, a preparation method and a medicine for treating pulmonary fibrosis, and belongs to the technical field of medicines. The demethylated cryptosterol separated from the fungus coniothyrium minitans has good anti-pulmonary fibrosis activity, and can be used as a lead compound for developing drugs for treating idiopathic pulmonary fibrosis. The invention provides an alternative compound for developing a new medicine for treating idiopathic pulmonary fibrosis, and has very important significance for development and utilization of natural product resources.

The invention discloses application of Psammatlysene D and a derivative thereof in preparation of a medicine for resisting chronic liver diseases, and belongs to the technical field of medicines. The technical scheme of the invention comprises the application of the Psammaglyene D in preparation of a product for resisting chronic liver diseases. The Psammatlyene D can inhibit the growth of LX2 cells, reduce liver function indexes ALT and AST, and relieve the degree of hepatic fibrosis in a mouse body; the growth of liver cancer cells can be inhibited in vivo and in vitro, and a synergistic effect can be generated with sorafenib; meanwhile, the anti-proliferation ability is also shown in sorafenib drug-resistant liver cancer. The derivative B12 of the Psammatlysene D has a stronger in-vitro anti-hepatic fibrosis effect, and the C11 has a very weak inhibition capability on hERG (human endothelial growth factor) and has no potential cardiotoxicity. The results show that the Psammaglyene D has relatively strong capabilities of resisting hepatic fibrosis, inhibiting liver cancer development and relieving sorafenib drug-resistant liver cancer, and the Psammaglyene D and C11 can be used as potential lead compounds for the development of anti-hepatic fibrosis and anti-liver cancer drugs, and are finally applied to the treatment of chronic liver diseases.

This invention discloses a heterozygous sesquiterpene tricyclic epoxy compound derived from the strain *Arthrum oligosporum*, its preparation method, and its applications, belonging to the field of natural product chemistry. This invention provides a heterozygous sesquiterpene tricyclic epoxy compound derived from *Arthrum oligosporum* (… A.oligospora ) AOL_ s00210g57 Anthrobotrisin D, a novel heterozygous sesquiterpene tricyclic epoxy compound from a gene knockout strain, has been shown in vitro to possess excellent anti-inflammatory activity, significantly inhibiting lipopolysaccharide-induced inflammatory responses in mouse microglia. It exhibits a clear dose-dependent inhibitory trend at multiple levels, including NO release, protein and mRNA expression of inflammatory factors (TNF-α, IL-1β, IL-6), and iNOS protein and mRNA expression. Furthermore, at a concentration of 33 μM, its anti-inflammatory effect is comparable to that of the clinically proven positive drug dexamethasone, and in some aspects, it is even superior. This invention not only provides a new lead compound for the development of anti-inflammatory drugs but also opens up new directions for developing new drugs from the unique microbial resource of nematode-preying fungi.

The present application relates to the technical field of microbial pesticides, in particular to a deep-sea streptomyces with antifeedant function and antibacterial effect and application thereof. The streptomyces from the South China Sea deep sea is Streptomyces sp. NA13, which was preserved in China Center for Type Culture Collection on August 29, 2022, and the preservation number is CCTCC M 20221343. The strain has the ability to prepare antibiotics such as Antimycin, Candicidin, Naringenin, Surugamide, Fredericamycin, SAL-2242, Albaflavenone, Hopene, SGR PTMs, etc. In particular, the fermentation is used to prepare antimycin or cyclic octapeptide surugamide compounds, including novel antimycin compounds antimycin Q (1). The prepared antimycin compounds are used as insect pest antifeedants or antifungal drug lead compounds, and have application prospects of developing into natural source antibacterial and insecticidal pesticides.

The invention relates to the technical field of traditional Chinese medicine extraction and separation, in particular to an extraction and separation method of a pyridine alkaloid compound in purslane and application of the pyridine alkaloid compound. The molecular formula of the pyridine alkaloid compound is C6H8N2O, and the pyridine alkaloid compound is named as 6-metaxyridin-3-amine. According to the method, ethyl alcohol reflux extraction, ODS column, Sephadex LH-20, a high performance liquid chromatograph and the like are adopted for separation, purification and preparation, 6-methoxyridin-3-amine is successfully extracted and separated, the method is easy to operate, the operation method is simple, convenient and rapid, ethyl alcohol and methyl alcohol are mainly adopted for extraction in the extraction and separation process, the technological method is environmentally friendly, and the method is suitable for industrial production. The purity of the compound separated by the method is higher than 99%, and research shows that the compound has an anti-inflammatory effect, so that the pyridine alkaloid compound and the salt and the derivative thereof can be used as synthesis primers of other compounds and raw materials for new drug development and pharmacological activity research, and can also be used for preparing anti-inflammatory drugs.

The application belongs to the technical field of agricultural chemistry, and particularly relates to a naphthoquinone compound with anti-tobacco black shank disease activity and a preparation method and application thereof. The naphthoquinone compound is extracted from honeysuckle branches with high-concentration methanol, high-concentration acetone / water or high-concentration ethanol / water, the extract is combined, filtered, and concentrated into an extract under reduced pressure; the extract is subjected to silica gel column chromatography by dry column packing with silica gel; gradient elution is performed with chloroform-acetone solution; and the 7:3 part of the eluate is further separated and purified by high-performance liquid chromatography to obtain the required naphthoquinone compound. The application also discloses the application of the compound. The active test shows that the compound has a good inhibitory effect on tobacco black shank disease. The compound has a novel structure, good anti-black shank disease activity, and can be used as a lead compound for anti-tobacco black shank disease and for the research and development of anti-tobacco black shank disease biological pesticides.

This application provides a method, system, device, and medium for lead compound design based on deep reinforcement learning. It innovatively achieves de novo design of covalent inhibitors targeting affinity, proposes an innovative method for constructing novel drug molecules based on multiple different bioactive fragments, and optimizes the model's exploration space. The application of the physics computation software Autodock-GPU as a scoring function enhances the model's generalization ability and running speed. The application of Munchausen reinforcement learning techniques to the Soft Actor Critic discrete action space model improves the model's optimization performance. Compared to other models, this application expands and improves upon the model's functionality and the properties of the generated molecules.

The invention relates to the technical field of medicines, in particular to an enantiomer-atesane type diterpenoid compound as well as a preparation method and an application of the enantiomer-atesane type diterpenoid compound. The enantiomer-atesane diterpenoid compound disclosed by the invention is derived from plants, has anti-tumor activity, has cytotoxicity to human leukemia cells, human liver cancer cells and human cervical cancer cells, and is relatively good in inhibitory activity. Wherein the compound 3 has the best effect, the IC50 values of the compound 3 to three human tumor cells are 7.5 + / -1.2 micromole per liter, 9.8 + / -1.0 micromole per liter and 10.1 + / -0.9 micromole per liter respectively, and the activity of the compound 3 is equivalent to that of a positive control drug mitomycin. Particularly, the compound 3 also has good cytotoxicity to drug-resistant liver cancer cells (Huh7-LR cells), and the IC50 value of the compound 3 is 9.6 + / -1.1 micromole per liter. The compound 3 shows huge potential as a lead compound by virtue of the novel chemical structure and potent cytotoxicity shown in various cell lines.

The invention belongs to the technical field of new applications of medicines, and particularly relates to an aniline pyridine TEAD degradation agent, a preparation method thereof and an application of the degradation agent in preparation of antitumor drugs. According to the research, a novel aniline pyridine TEAD degradation agent with a clear structure is designed and synthesized by coupling a TEAD palmitoylation inhibitor niflumic acid serving as a lead compound with a CRBN type E3 ligase ligand through connecting chains with different lengths and different types by virtue of a computer-aided drug design means. The influence of the optimal compound (XY-3L) on cancer cell proliferation and cell functions is detected in an in-vitro cell experiment, and the curative effect of the optimal compound (XY-3L) in a melanoma lung metastasis model is explored in vivo.

The invention provides a rehmannia pigment compound as shown in a formula (I), a stereoisomer thereof or pharmaceutically acceptable salt thereof, and particularly relates to the technical field of natural pharmaceutical chemistry and pharmaceutical compounds. The invention aims to solve the problems that the radix rehmanniae pigment is not clear in material basis and lacks a compound with a clear structure and excellent anti-inflammatory activity. The rehmannia pigment compound disclosed by the invention comprises a structure as shown in a formula (I). The invention also discloses a preparation method of the compound and application of the compound in medicines. The compound has a novel chemical structure and remarkable anti-inflammatory activity, release of nitric oxide can be effectively inhibited in a lipopolysaccharide induced macrophage model, the cytotoxicity is far lower than that of a positive control drug quercetin, and the compound shows huge potential as an anti-inflammatory drug lead compound.

The application discloses a tobacco endophytic fungus metabolite, a preparation method and application in tobacco alternaria alternata prevention and treatment, and relates to the technical field of microbial natural product pesticides. The tobacco endophytic fungus metabolite is a benzoquinone compound peniquinone L, and a structural formula is as follows: The benzoquinone compound peniquinone L is produced by fermentation of tobacco endophytic fungus Aspergillus aculeatus Aspergillus aculeatus Aa-1, and scale fermentation and preparation production are easy to carry out. The tobacco endophytic fungus metabolite benzoquinone compound peniquinone L of the application has inhibitory activity on various agricultural pathogens, and has significant bacteriostatic activity on tobacco alternaria alternata in particular, with an MIC value of 2 μg / mL, which is superior to positive drug carbendazim, and can be used as a leading compound or a new microbial natural product pesticide for tobacco alternaria alternata prevention and treatment.