A kind of anti-acute myeloid leukemia compound and its preparation method and application
A compound and composition technology, which are applied to compound A-Z2 and its preparation and application in anti-acute myeloid leukemia, can solve problems such as damage to human organs, achieve less toxic and side effects, reduce toxicity, and promote targeted inhibition Effect
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Embodiment 1
[0045] [Example 1] The synthetic method of drug precursor Z2 and A-Z2
[0046] 1. Synthesis of Z2
[0047] Add p-aminophenylarsenic acid to 70% ammonium thioglycolate, and mix thoroughly according to the molar ratio of 120:18; after stirring at 50°C for 2 hours, add 1,3-propanediol dropwise in an amount of 23 moles compared to the same amount. Then the turbid solution was extracted with DCM for 24 min×10 times. The DCM solution was concentrated by silica gel column chromatography (PE / DCM=1 / 1, v / v) to obtain Z2 with a product yield of 52%.
[0048] 2. Synthesis of A-Z2
[0049] Azelaic acid was mixed with hydrochloride (EDCI), 1-hydroxybenzotriazole (HOBt) and N,N-diisopropylethylamine (DIPEA) in a molar ratio of 10:15:15:2, and used After 10mL of tetrahydrofuran was completely dissolved, it was stirred at room temperature for 2-4h. Then 2 molar amounts of Z2 were added to the solution. After standing for 4 hours, the product A-Z2 was separated and purified by silica gel c...
Embodiment 2
[0053] [Example 2] CCK-8 method was used to detect the inhibition of drug on cell proliferation.
[0054] AML cells (THP-1, MOLM-13, HL60) were planted on the 96-well plate, each 100 μL 6×10 4 1 / mL cells, add 0, 1, 10, 100, 1000, 2000, 4000, 8000nM A-Z2 10μL each, add 10μL of CCK-8 detection solution 24, 48, 72h after drug treatment, and detect at 450nm Absorbance.
[0055] like figure 2 As shown in A, A-Z2 inhibited the viability of these cells in a dose- and time-dependent manner.
[0056] Healthy human peripheral blood mononuclear cells (PBMC) and normal mouse stem cells AML 12 cells were inoculated on a 96-well plate, 1×10 per well 4 cells, add 1 μM A-Z2, Ara-C, As 2 o 3 (ATO) treatment for 24h to detect cell viability in each well.
[0057] like figure 2 As shown in B, A-Z2 is better than Ara-C and As 2 o 3 Less toxic side effects on normal cells.
Embodiment 3
[0058] [Example 3] Flow cytometric detection of the effect of AZA on the cell cycle and apoptosis of AML cells
[0059] Will 1×10 5 -1×10 7 Put the cells into a 1.5ml EP tube and centrifuge at 3000r / min for 5min, discard the supernatant, add 100μL of PBS to suspend the cells, add Annexin-V / PI staining, incubate at 4℃ for 45min, after A-Z2 treatment for 24h, collect and resuspend all The cells were in 100ml of buffer solution, and the effects of A-Z2 on cell cycle and apoptosis were detected by flow cytometry.
[0060] like image 3 As shown in A, A-Z2 can promote the apoptosis of AML cells;
[0061] like image 3 As shown in B, A-Z2 can arrest AML cells in G2 / M phase;
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