Application of securinine linked dimeric compound SN3-L6 or pharmaceutical salt thereof in preparation of anti-leukemia drugs

A technology of SN3-L6 and hagiline chain, applied in the field of medicine, can solve the problems of limited validity period, improper platelet preservation method, and insufficient supply of platelets, etc., and achieve the effect of inhibiting cell proliferation and improving medicinal prospects.

Pending Publication Date: 2021-01-19
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, all clinically transfused platelets are obtained from volunteer donations. In the United States, 1×10 platelets need to be transfused every year. 6 Unit platelets, limited sources of platelet donations, improper platelet storage methods and limited validity period lead to an obvious shortage of clinic

Method used

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  • Application of securinine linked dimeric compound SN3-L6 or pharmaceutical salt thereof in preparation of anti-leukemia drugs
  • Application of securinine linked dimeric compound SN3-L6 or pharmaceutical salt thereof in preparation of anti-leukemia drugs
  • Application of securinine linked dimeric compound SN3-L6 or pharmaceutical salt thereof in preparation of anti-leukemia drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Inhibitory effect of SN3-L6 on proliferation of leukemia cell HL60

[0042] (1) Experimental method: Take HL60 cells (purchased from Sun Yat-Sen University Cell Bank) in logarithmic phase growth, inoculate in 25cm 2 Cell culture flask, 15,000 / mL, 10mL / bottle. Add the final concentration of 7.5μM SN3-L6 and an equal volume of DMSO (dimethyl sulfoxide, the final concentration of which should be controlled below 0.1% (v / v)) for treatment, put them into a constant temperature cell incubator, and change them every two days solution and add medicine once, cell counting is carried out every two days (dilution culture is carried out when the cell density is greater than 500,000), and the cell growth curve is drawn, such as figure 1 shown.

[0043] (2) Test results: SN3-L6 can significantly inhibit the proliferation of HL60 cells.

Embodiment 2

[0044] Example 2 Wright's-Giemsa staining of HL60 cells after SN3-L6 treatment

[0045] (1) Experimental method: Take HL60 cells grown in logarithmic phase, inoculate in 6-well plate, 50,000 / well, 2mL / well, add SN3-L6 with a final concentration of 10 μM and an equal volume of DMSO (final concentration control (below 0.1% (v / v)) for 3 days and 6 days respectively, collect the cell suspension and centrifuge on the 3rd or 6th day, discard the supernatant, then add PBS (PBS buffer, pH 7.4) to resuspend and centrifuge again Collect the cell pellet and wash repeatedly three times to collect the cells. Finally, 200 microliters of PBS was added to resuspend the cells, spread on a glass slide soaked in paraformaldehyde and dried in the air, so that the cells were evenly distributed in a single layer on the glass slide. Add 1000 microliters of Giemsa-Wright's staining solution A to the cell area on the slide, and at the same time gently blow the staining solution with the ear washing b...

Embodiment 3

[0047] Example 3 Flow cytometric detection of HL60 cells after SN3-L6 treatment

[0048] (1) Experimental method: HL60 cells in the logarithmic growth phase were inoculated in 6-well plates, 100,000 cells / well, and SN3-L6 with a final concentration of 7.5 μM and an equal volume of DMSO were added (the final concentration was controlled at 0.1% ( v / v) below) after treating HL60 cells for 6 days, collect the cells by centrifugation, wash with PBS three times and then detect the cell signal by flow cytometry, the results are as follows image 3 shown.

[0049] (2) Test results: After 7.5 μM SN3-L6 was applied to HL60 cells, the FSC value on the abscissa moved significantly to the right, indicating that the cells were significantly larger, and the SSC value on the ordinate moved significantly upward, indicating that the complexity of the granules inside the cells also increased significantly.

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Abstract

The invention discloses an application of a securinine linked dimeric compound SN3-L6 or pharmaceutical salt thereof in preparation of anti-leukemia drugs. It is found that the SN3-L6 has a relativelygood in-vitro anti-leukemia effect, and can obviously inhibit the proliferation of acute myeloid leukemia cells; the SN3-L6 can induce the cells to transdifferentiate into megakaryocytes and then induce the megakaryocytes to generate platelets, so that the SN3-L6 has a good medicinal prospect in the aspects of acute myeloid leukemia transdifferentiation treatment and in-vitro platelet generation;and the SN3-L6 can also induce transdifferentiation of chronic erythroleukemia cells into megakaryocytes and then induce apoptosis of the megakaryocytes, so that the SN3-L6 also has a good medicinalprospect in the aspect of chronic erythroleukemia treatment.

Description

technical field [0001] The invention belongs to the field of medicines, and in particular relates to the application of the monophyllin chain-linked dimer compound SN3-L6 or a medicinal salt thereof in the preparation of anti-leukemia drugs. Background technique [0002] Leukemia is a malignant clonal disease of hematopoietic stem cells, characterized by uncontrolled proliferation, impaired differentiation, and blocked apoptosis. Acute myeloid leukemia is the fastest-onset type of leukemia, and acute promyelocytic leukemia is the most dangerous type of acute myeloid leukemia. Acute promyelocytic leukemia is currently mainly treated with all-trans retinoic acid-induced differentiation, but long-term treatment with all-trans retinoic acid will also cause obvious side effects and drug resistance, such as increased risk of coagulation disorders, all-trans retinoic acid Syndrome, occurrence of septic arthritis, etc. :1193-1194). At present, no new leukemia differentiation indu...

Claims

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Application Information

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IPC IPC(8): A61K31/55A61P35/02
CPCA61K31/55A61P35/02
Inventor 陈卫民林静侯文叶文才
Owner JINAN UNIVERSITY
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