Thiophene and benzothiophene hydroxamic acid derivatives
A phenyl and compound technology, applied in the field of hydroxamic acid derivatives with benzothiophene or thiophene skeleton, can solve the problems of excessive proliferation of leukemia cell lines, inability to complete differentiation of tumor cells, etc.
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Embodiment 2
[0948] Example 2 - Inhibitory effect of novel compounds on HDAC
[0949] HDAC1-Flag test:
[0950] The ability of novel compounds to inhibit histone deacetylase, isoform 1 (HDAC1) was determined using an in vitro deacetylation assay. The enzyme source used for this test was epitope-tagged human HDAC1 obtained from immunopurified cells stably expressing mammalian cells. The substrate consisted of a commercial product containing acetylated lysine side chains (BIOMOL Research Laboratories, Inc., Plymouth Meeting, PA). After deacetylation of the substrate by incubation with purified HDAC1 complex, a fluorophore commensurate with the level of deacetylation is generated. The concentration of the substrate used in the enzyme preparation was Km, and the deacetylation test was performed with increasing concentrations of novel compounds to semiquantitatively determine the concentration of the compound required to inhibit 50% of the deacetylation reaction (IC50).
[0951] result:
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Embodiment 3
[0984] Example 3 - HDAC Inhibition in Cell Lines
[0985] MTS test
[0986] The novel compounds of the present invention were tested for their ability to inhibit the proliferation of the murine erythroleukemic cell line SC9.
[0987] MTS assay, also known as Cell Titer 96 Aqueous One Solution Cell Proliferation Assay (96-well cell titer plate single aqueous solution cell proliferation assay), is a colorimetric method for determining the number of living cells in proliferation, cytotoxicity or chemical sensitivity analysis. MTS reagent contains a novel tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H - tetrazolium, inner salt] and electron coupling reagent (phenazine ethyl sulfate; PES). Murine erythroleukemia cells (SC-9) were incubated with vehicle or increasing concentrations of compounds for 48 hours. Cell proliferation was quantified by adding a small amount of MTS reagent directly to the culture wells, incubating for 1-...
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