9 results about "Aporphine" patented technology

The application belongs to the technical field of medicines, and relates to an N-H aporphine nitrogen-containing heterocyclic derivative, a preparation method and application thereof.The N-H aporphine nitrogen-containing heterocyclic derivative comprises a compound shown in a general formula M, isomers thereof and pharmaceutically acceptable salts or hydrates thereof.The application introduces a nitrogen-containing heterocyclic ring into an aporphine derivative, and the disclosed N-H aporphine nitrogen-containing heterocyclic derivative can be applied in the preparation of medicines for preventing and / or treating obesity, urinary incontinence, depression, anxiety, obsessive-compulsive disorder, epilepsy, schizophrenia, pain, diabetes and drug addiction.

The invention discloses a method for producing aporphine alkaloid and recombinant bacteria used by the method. According to the invention, the synthetic route of the aporphine alkaloid is divided into four modules for research, and the de novo synthesis of the aporphine alkaloid is realized through various strategies; wherein the original strain is an IMX581 yeast strain. Experiments prove that the engineering strain constructed by the invention can be used for efficiently producing aporphine alkaloids such as (R)-croflorin, (R)-glaziovine, (S)-glaziovine, magnoflorin and the like. The aporphine alkaloids disclosed by the invention can be used for efficiently producing aporphine alkaloids such as (R)-croflorin, (R)-glaziovine, (S)-glaziovine, magnoflorin and the like. The method has an important application value.

The invention relates to an aporphine-benzylisoquinoline alkaloid dimer as well as a preparation method and application thereof, and belongs to the field of natural medicines and biological medicines. The aporphine-benzylisoquinoline alkaloid dimer has a structural general formula shown in the specification, in the formula, R1, R2, R3, R4, R5, R6, R7 and R8 are independently selected from hydrogen, methoxyl, hydroxyl or two adjacent substituent groups are methylenedioxy, so that a five-membered ring is formed; and R9 is selected from hydrogen, methoxyl or hydroxyl. Six novel aporphine-benzylisoquinoline alkaloid dimers are extracted and separated from roots of thalictrum omeiensis, and through detection, the aporphine-benzylisoquinoline alkaloid dimers have obvious growth inhibition effects on human acute promyelocytic leukemia cells HL-60 and human prostate cancer cells PC-3, and have the prospect of preparing medicines for preventing and treating tumors.

The invention discloses a chemical enzyme synthesis method of chiral aporphine alkaloids, and relates to the field of biochemistry, the method comprises the following steps: taking a phenylethylamine compound and a phenylacetic acid compound as initial raw materials, and carrying out amide condensation and dehydration cyclization to form a compound IV; then reducing through imine reductase or an imine reductase mutant to form a V-type compound; then, a compound VI is formed through a methylation reaction of methyltransferase or Eschweiler-Clarke or methyl iodide, and the compound VI is formed through a methylation reaction of methyltransferase or Eschweiler-Clarke or methyl iodide; and finally, carrying out photocatalytic coupling to obtain the aporphine alkaloid. According to the preparation method disclosed by the invention, purification is not needed in the preparation reaction process from the IV-type compound to the VI-type compound, and the compound can be directly used for the last step of photocatalytic coupling; the optically pure (S)-VII aporphine alkaloid can be obtained; the method is mild in reaction condition, green, environment-friendly, simple in process, low in cost, capable of reaching gram-level scale and suitable for industrial production.

The application discloses a cytochrome P450 enzyme derived from Stephania sinica Diels and application thereof in biosynthesis of aporphine alkaloid compounds. The application first characterizes a key P450 involved in formation of a methylenedioxy bridge structure of aporphine alkaloids in Stephania sinica Diels, provides an important reference for analysis of an aporphine alkaloid biosynthesis pathway in other species, and lays a foundation for heterologous production of various aporphine alkaloids. The application screens a P450 enzyme CYP719C3 annotated as CYP719 in a genome of Stephania sinica Diels, performs enzymatic reactions with different aporphine compounds as substrates, and detects reaction results by using a liquid chromatograph-mass spectrometer. It is found that CYP719C3 can catalyze an enzyme forming a methylenedioxy bridge on an A ring of an aporphine alkaloid, and can be applied to further analysis and heterologous production of an aporphine alkaloid pathway.

The invention discloses application of aporphine alkaloid Tinopaine A in hemsleya amabilis ox gall in preparation of a medicine for treating bone destruction related diseases, and belongs to the technical field of biological medicine. Experiments prove that the Tinpaine A monomer has an inhibition effect on osteoclast differentiation formation in vivo and in vitro; by regulating and controlling key factors for osteoclast formation, the compound has an inhibiting effect on in-vitro osteoclast formation under the concentration of 1-10 mu M and on in-vivo osteoclast formation of mice under the dosage of 2-20 mg / kg, can effectively reduce the number of osteoclasts and protect bone trabecula structures, and has an excellent treatment effect on bone destruction related diseases. The invention relates to a medicine for inhibiting osteoclast differentiation in vivo and in vitro and treating diseases related to bone destruction, which takes Tinopaine A as an active ingredient and can relieve bone destruction by regulating and controlling bone metabolism balance so as to achieve the purpose of treating the diseases related to bone destruction.

The invention belongs to the technical field of medicines, and finds that aporphine alkaloids, especially magnoline and nuciferine, can reduce the BUN level and SCr level of a cisplatin-induced acute kidney injury model mouse through a large number of experimental screening, can obviously relieve cisplatin-induced kidney function impairment, and can be used for preparing medicines for treating acute kidney injury. The compound can be used as a medicine for reducing adverse reaction of renal function impairment caused by cis-platinum.

The invention discloses a chemical enzyme preparation method and application of alkaloid, and belongs to the technical field of bioengineering. According to the invention, the (S)-tetrahydropapaverine and the derivative thereof are efficiently synthesized by utilizing an artificially designed multi-enzyme cascade reaction, and tetrahydroprotoberberine, aporphine, morphine dienone alkaloid and the derivative thereof are synthesized by using a chemical method. According to the invention, key enzymes of a synthetic route are respectively expressed in escherichia coli BL21, BL21-1, BL21-2 and BL21-3 are constructed, and (S)-tetrahydropapaverine and derivatives thereof are synthesized by using the strains. The (S)-tetrahydropapaverine and the derivative thereof prepared by the method disclosed by the invention can be further catalytically synthesized into alkaloids such as tetrahydroprotoberberine, aporphine and morphine dienone through a chemical method, and the (S)-tetrahydropapaverine and the derivative thereof have a wide application prospect.

The application discloses a use of an aporphine alkaloid shown in formula III in preparation of an antidepressant, wherein R1 and R2 are independently selected from alkoxy and methylenedioxy, R3 and R4 are independently selected from H, OH, alkoxy and methylenedioxy, but R3 and R4 cannot be H at the same time or R1 and R2 are both selected from methoxy, and R3 cannot be OH and R4 cannot be H. Pharmacological experiments show that the aporphine alkaloid shown in formula III has better antidepressant effect, higher response rate and faster effect than fluoxetine.