Anti-human triple negative breast cancer activity of a CA-4 derivative
Objective To design and synthesize a CA-4 derivative[1-(3,5-difluorophenyl)-2-(6-methoxy-2-(1-(3,4,5-trimethoxyphenyl)vinyl)benzofuran-5-yl)ethylene]based on the microtubule and PI3K protein as dual targets,using CA-4 as the lead compound,and to preliminarily study the PI3K activity was on human triple negative breast cancer cell line MDA-MB-231.Methods MTT was used to measure IC50 value,inverted microscope to observe the cell state,flow cytometry to detect cell cycle arrest,AutodockTools system to dock the derivative and PI3K molecule,ELISA to detect PI3K secretion in the cell supernatant,and RT-PCR and Western blot to detect PI3K mRNA and protein expression levels,respectively.Results The IC50 was 5.78 μmol·L-1.Many morphological apoptotic changes occurred,and the cell growth cycle was hindered in G2 phase.Derivatives bound well with PI3K(-36.4008 kJ·mol-1),the PI3K secretion decreased,and gene and protein expression levels were down-regulated.Conclusion The PI3K target activity of the derivative has been verified,providing a reference for further mechanism research of this type of derivative.
combretastatin A-4triple negative breast cancerPI3K
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