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Natural naphthyl isoquinoline compounds with antitumor activity and their compositions and applications

A compound and tumor technology, applied in the field of biomedicine, can solve the problems of treatment failure and no obvious prolongation of patient survival, and achieve the effect of wide application prospects

Active Publication Date: 2021-01-29
DALIAN NATIONALITIES UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, reversible and irreversible EGFR-TKIs have a significant curative effect on mutant EGFR non-small cell lung cancer in a short period of time, but in the end they all lead to treatment failure due to acquired drug resistance, and did not significantly prolong the survival of patients

Method used

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  • Natural naphthyl isoquinoline compounds with antitumor activity and their compositions and applications
  • Natural naphthyl isoquinoline compounds with antitumor activity and their compositions and applications
  • Natural naphthyl isoquinoline compounds with antitumor activity and their compositions and applications

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Experimental program
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Effect test

Embodiment 1

[0040] The preparation of embodiment 1 naphthyl isoquinoline compound molecule

[0041] (1) Alcohol extraction step: take freshly dried branches and leaves of Ancistrocladus tectorius, crush them, extract 3 times with 10 times the amount of 95% ethanol solution, each time for 0.5h, and concentrate the extract under reduced pressure below 50°C , make the extract, reclaim the solvent ethanol, and obtain the ethanol extract of Uncaria twig branches and leaves;

[0042](2) Extraction step: add 0.3 times the weight of water to the extract of the ethanol extract of Uncaria vine branch and leaf, disperse and dissolve, then use cyclohexane and dichloromethane to extract and extract twice respectively to obtain the cyclohexane extraction part and dichloromethane extraction site;

[0043] (3) Diol-based chromatographic column chromatography step: get the dichloromethane extraction part, pack it on the Diol-based chromatographic column of 30 times its weight, and use 3 times of column v...

Embodiment 2

[0046] The preparation of embodiment 2 naphthyl isoquinoline pharmaceutical compositions

[0047] Take equimolar amounts (1 mmol) of the above two target molecules in anhydrous methanol (5 mL), stir at room temperature for 10 minutes, evaporate the solvent at room temperature, and obtain a mixture of target molecules. Three mixtures (I-1)-(I-2), (I-3)-(I-8), and (I-7)-(I-10) were prepared by this method.

Embodiment 3

[0048] Embodiment 3 naphthyl isoquinoline compound anti-cell proliferation activity

[0049] The anti-proliferation activity of naphthylisoquinoline monomer compounds in vitro on non-small cell lung cancer cells was determined by MTT method. Select EGFR WT Highly expressed A549 cells, EGFR T790M Highly expressed H1975 cells and HCC827 cells with EGFR sensitive mutations were tested for their proliferation inhibitory activity. During the determination, PBS was used as blank control, and gefitinib and rolectinib were used as positive controls.

[0050] (1) Cell culture: Human non-small cell lung cancer cell lines (A549, H1975, HCC827) were cultured in RPMI 1640 medium containing 10% fetal bovine serum and 1% double antibody at 37°C, 5% CO 2 cultured in an incubator.

[0051] (2) Cell inoculation: take cells in good condition in the exponential growth phase, collect the cells and centrifuge, and discard the supernatant. Prepare the cell suspension with RPMI 1640 (or DMEM) cu...

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Abstract

The invention belongs to the field of biomedicine, and relates to natural naphthylisoquinoline compounds having antitumor activity, a composition of the compounds and an application of the compounds and the composition. The compounds are obtained by linking 1-site, 3-site, or 8-site of one compound represented by a general formula I and 5-site of one compound represented by a general formula II, or linking 1-site, 3-site, 6-site, or 8-site of the compound represented by the general formula I and 7-site of the compound represented by the general formula II, wherein the structures of the generalformula I and II are shown in the description. The compounds and the composition provided by the invention inhibit epidermal growth factor receptor tyrosine kinase (EGFR) for treating and / or preventing neoplastic diseases, particularly for treating non-small cell lung cancer or small cell lung cancer, can be developed into a novel EGFR-TKI, and have broad application prospects.

Description

technical field [0001] The invention relates to a natural naphthyl isoquinoline compound with antitumor activity, its composition and application, and belongs to the technical field of biomedicine. Background technique [0002] Protein tyrosine kinases (PTKs) regulate a series of physiological and biochemical processes such as cell growth, differentiation, and apoptosis by controlling cell signal transduction pathways. Receptor-type tyrosine kinases are a relatively large class of kinases that span cell membranes, possess a ligand-binding extracellular domain, a transmembrane domain, and act as kinases—in phosphorylating specific tyrosine residues and by This affects the intracellular domain of cell proliferation. Aberrant expression of these kinases has been found in common human cancers (eg, lung cancer, breast cancer, gastric cancer, ovarian cancer, lymphoma). Protein tyrosine kinase has become one of the important targets in the research and development of anticancer d...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D217/02A61K31/472A61P35/00C07D217/04
CPCA61K31/472A61P35/00C07D217/02C07D217/04
Inventor 李珂珂弓晓杰门磊李春斌石玉生
Owner DALIAN NATIONALITIES UNIVERSITY