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Natural maytansine compound and application thereof in pharmacy

A technology of maytansine derivatives and compounds, which is applied in the field of medicine, and can solve the problems of insufficient research on the chemical components of guacamole

Pending Publication Date: 2022-07-29
FUDAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the research on the chemical constituents of the slide peach tree is not sufficient, and the maytansinoids in it need to be further studied

Method used

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  • Natural maytansine compound and application thereof in pharmacy
  • Natural maytansine compound and application thereof in pharmacy
  • Natural maytansine compound and application thereof in pharmacy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Example 1 Extraction of the compound of the present invention from Peach tree

[0016] (1) Extraction: pulverize the dried peach tree fruit (10.7 kg), percolate and extract with 95% ethanol at room temperature, concentrate under reduced pressure to obtain an extract, and disperse the extract in water with ethyl acetate. Extraction, recovery of solvent under reduced pressure, and concentration to dryness to obtain 420 g of ethyl acetate extract;

[0017] (2) Separation: 420 g of the ethyl acetate extract was subjected to macroporous resin HP-20 column chromatography, and ethanol-water (30:70→45:55→60:40→75:25→90:10→100 : 0) gradient elution, the amount of each gradient is 50 liters, and the fractions are collected; wherein the macroporous resin ethanol-water 60:40 fraction (43.2 g) is subjected to silica gel column chromatography, and dichloromethane-methanol (30:1 →15:1→10:1→8:1→5:1→2:1→1:1) Gradient elution, the amount of each gradient is 5 liters; the dichloromethane...

Embodiment 2

[0024] Inhibitory effect test of compounds of formula (I) and (II) on the proliferation of tumor cell lines HeLa, MV-4-11, MCF-7, MCF-7 / ADR

[0025] The compounds of formula (I) and (II) were tested by tetramethylazolium salt (MTS) colorimetric method on four tumor cell lines HeLa (cervical adenocarcinoma cell line), MV-4-11 (human myeloid mononuclear cell line) Cell leukemia cell line), MCF-7 (human breast cancer cell line), MCF-7 / ADR (human breast cancer adriamycin-resistant cell line) cell proliferation inhibition (ACS MedicinalChemistry Letters 2018,9,502.);

[0026] at 37°C and 5% CO 2 The cells were subcultured under the following conditions, and the cells in the logarithmic growth phase were selected, the medium was aspirated, and the cells were counted by gently pipetting and counting at 5 × 10 4 The cell density was seeded in a 96-well plate, and 90 μL was seeded in each well, and 10 μL of compound was added. Each compound was set up with a concentration gradient, an...

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Abstract

The invention belongs to the technical field of medicines, and relates to a natural maytansine compound separated from silene tunicoides and application of the natural maytansine compound in pharmacy. The present invention relates to a compound of formula (I), in particular to a compound of formula (I), i.e., a 4, 24-dioxa-9, 22-diaza tetracyclo [19.3.1. 110, 14.03, 5] hexacosanmaytansine derivative, and to a compound of formula (II), i.e., N-methylterrilaroline, i.e., a 3, 7, 30-trioxa-9, 22, 27-triaza pentacyclo [20.8. 2.16, 10.117, 21.02, 4] tetradecane terrilaroline derivative, in particular to a compound of formula (I), i.e., a 4, 24-dioxa-9, 22-diaza tetracyclo [19.3.1. 110, 14.03, 5] hexacosanmaytansine derivative. The compound is extracted from dry fruits of peach trees, and tests prove that the compound has very strong anti-tumor activity and can be used for preparing anti-tumor drugs, especially drugs for resisting human cervical cancer, human leukemia and human breast cancer.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a natural maytansine compound isolated from Peach tree and its use in pharmacy. Specifically related to the compound methyltrewiasine (methyltrewiasine, namely 4,24-dioxa-9,22-diazatetracyclo[19.3.1.1] 10,14 .0 3,5 [ 20.8.2.1 6,10 .1 17,21 .0 2,4 ] tetratetradecane terrifaroline derivatives) and its use in the preparation of antitumor drugs. Background technique [0002] The prior art discloses that Maytansine (Maytansine) is a macrocyclic lactam compound, which was first discovered in 1972 from Maytenus ovatus and is a natural antitumor active ingredient (Journal of the American Chemical Society). 1972, 94, 1354.). A variety of analogs of maytansine and Ansamitocins found from microorganisms have been successively discovered from the genus Maytansin, collectively referred to as Maytansinoids. In early 2013, the first maytansine antibody conjugated drug (Kadcyla) was appro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/18C07D498/22A61P35/00
CPCC07D498/18C07D498/22A61P35/00
Inventor 侯爱君李佳雷春周宇波
Owner FUDAN UNIV