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Polyketone compound as well as preparation method and application thereof

A compound, polyketone technology, applied in the field of medicine, can solve problems such as unreported

Active Publication Date: 2016-10-19
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Macrocyclic polylactone compounds have been reported to have antifungal and nerve growth factor promoting effects, but their antitumor activity, especially the growth inhibitory effect on leukemia cell lines, has not been reported at home and abroad

Method used

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  • Polyketone compound as well as preparation method and application thereof
  • Polyketone compound as well as preparation method and application thereof
  • Polyketone compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Pick the spores of the fungus of the genus Ascotricha (Ascotricha sp.ZJ-M-5, the preservation number is CGMCC No.8278), and directly inoculate them into a liquid medium for static culture for 28 days, wherein the medium is prepared by distilled water and contains sucrose 3%, NaNO 3 0.3%, CaCl 2 0.46%, KCl 0.05%, FeSO 4 ·7H 2 O 0.001%, K 2 HPO 4 0.1%, the culture temperature is 25°C. After the fermentation product is filtered to remove the fermentation broth, the mycelium is ultrasonically extracted 3 times with acetone, the extract is combined and the solvent is recovered, and then separated by 3 times the amount of 200-300 mesh silica gel column chromatography, and the volume ratio is 5:1-1: 1 petroleum ether-acetone mixed solvent gradient elution, wherein the volume ratio of 3:1 petroleum ether-acetone mixed solvent elution part is purified by Sephadex LH-20 column chromatography with methanol as the eluent to obtain the compound of formula I , the yield is 12mg...

Embodiment 2

[0031] Embodiment 2: The growth inhibition test of the compound of formula I to human acute promyelocytic leukemia HL-60 cell line and human leukemia K562 cell line in vitro:

[0032] HL-60 or K562 cells were cultured in RPMI1640 medium containing 10% heat-inactivated fetal bovine serum, 100 IU / mL penicillin, 100 μg / mL streptomycin and 1 mmol / L L-glutamine at 37°C. 5%CO 2 Incubate in a saturated humidity incubator until the cells are 70%-80% confluent. Weigh trypan blue, add a small amount of distilled water to grind, add double distilled water to dilute to 4% storage concentration, filter with filter paper, and store at 4°C. For use, this stock solution was diluted to a working concentration of 0.4% with PBS. Take HL-60 or K562 cells to 3×10 4 Cells / mL density, 1 mL per well was inoculated in a 24-well plate, and then added different concentrations of drugs or positive control drugs (final concentrations were 0.1, 0.5, 1, 3, 10, 30, 100 μM), and the control group was added...

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Abstract

The invention belongs to the field of medicine technology, and relates to a polyketone compound with antitumor activity which is separated from a strain of Ascotricha sp. and a preparation method thereof. The compound has a novel structure, and has substantial effects for inhibiting growth of a human acute promyelocytic leukemia HL-60 cell line and a human leukemia K562 cell line; a fermentation process as well as an extracting and separation method are simple, which are good for carrying out further pharmacological and clinic researches, and developing applications to preparation of medicaments for preventing and treating leukemia.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a polyketide compound which can inhibit the growth of human leukemia cell lines and its Preparation. Background technique [0002] Microorganisms can produce secondary metabolites with novel structures and diverse biological activities such as anti-tumor and anti-infection. Therefore, finding drug lead compounds from microorganisms has always been a hot spot in innovative drug research. Traditional microbial culture adopts the method of providing rich nutrients to promote its production. However, under this condition, the genes for the synthesis of secondary metabolites of most microorganisms are in a silent state, resulting in a small number and low content of secondary metabolites produced , and often produce many inactive substances such as fatty acids and cyclic dipeptides that interfere with extraction and separation. In view of this, Axel Zeeck et al. proposed the OSMAC (o...

Claims

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Application Information

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IPC IPC(8): C07D323/00C12P17/08A61K31/365A61P35/02C12R1/645
CPCC07D323/00C12P17/08
Inventor 李占林华会明王文静张金玲李丹毅
Owner SHENYANG PHARMA UNIVERSITY
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