Design And Synthesis Of A NIR Fluorescent Probe Based On Histone Deacetylase (HDAC)

In recent years,the incidence and mortality of malignant tumors are still rising,and cancer as one of the most world difficult problem is still hard to conquer.Histone deacetylase(HDAC)is frequently overexpressed in various cancer cells.It plays an important role in the regulation of genes transcription and functional proteins.HD AC has gained major interest as therapeutic and diagnostic target,mainly in cancer research.Giving into the key role of HD AC in tunor cells,we designed and synthesized a novel HDAC-targeted near infrared(NIR)fluorescent probe.Based on a recent report on HuDa dye,which has excellent optical property,we made a simple structure reconstruction on it.Without affecting the spectral property,we designed a novel HDAC-targeted NIR fluorescent probe via introducing the pharmacophore of the HDAC inhibitor SAHA to HuDa dye.In order to verify its targeting ability,we synthesized a near infrared dye by removing the Zinc-binding group(ZBG),which had the same optical property as the probe.Through the HDAC inhibition assay,the inhibition activity of the probe was verified.MDA-MB-231 cell and HeLa cell with HD AC overexpression,we did the cytotoxicity experiment and fluorescence imaging experiment using the two tumor cells.The probe displayed moderate intensity of cytotoxicity in HeLa cell.Through comparing the fluorescence intensity of the two cells incubated in two compouds,it showed the targeting ability of the probe from qualitative and quantitative and the characteristic of intracellular retention.In this paper,we designed and synthesized a near-infrared fluorescent probe H-A with good optical properties,which can well target to histone deacetylase conveniently and it can be applied to screening of HD AC inhibitors.According to the intracellular retention of HD AC inhibitors discoveried in biological experiments,we can designed the prodrugs targeting HD AC of antitumor drug.