Synthesis And Study On Physiological Activity Of Acenaphthopyrazine Derivatives

There is important meaning for developing new antineoplastic drugs that are low toxicity and high selectivity. It researches on DNA-target small organic compounds, the interaction with compound and DNA, and its influence on cell cycle and apoptosis. Based on design theories of DNA intercalators, a series of novel acenaphthopyrazine derivatives 1 was designed. These compounds possess a planar and rigid chromophore which carry one flexible basic side chains and two cyano groups on.Compounds 1 were synthesized from acenaphthylene-1,2-dione via three steps including bromization, cyclization, and SNArH reaction. The in vitro cytotoxic potencies of the new compounds against MCF-7 cells (human breast cancer cells) were evaluated by MTT tetrazolium dye assay, la (3-(2-Dimethylamino-ethylamino)-acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile) and 1g (3-morpholin-4-yl-acenaphtho[1,2-b]pyrazine-8,9-dicarbonitrile) show better antitumor activities in vitro, the IC50 value of 1a and 1g against MCF-7 cells is 4.60 and 6.46μM. In order to confirm the DNA-binding properties of these compounds, UV-vis absorption spectra, fluorescent spectra, circular dichroism spectra (CD), and viscosity titration were performed with calf-thymus DNA (CT-DNA). The DNA-binding experiments suggested that these derivatives bind to DNA through intercalation with the K (intrinsic binding constants) all above 105 M"1 and these compounds are actually moderate DNA-intercalators.Absorption and fluorescence spectrum studies indicated that these compounds have long emission wavelength (λem>560 nm), high quantum yields in toluene (Φf=0.59 for 1g) and large stocks shift (ΔS>130 nm), so they perhaps have potential application as fluorescent sensors and photoelectricity material.Fluorecence sensors S-1 (6-[2-(Bis-pyridin-2-ylmethyl-amino)-phenylamino]-2-butyl-benzo[de]isoquinoline-1,3-dione) and S-2 (6-[2-(2-Dimethylamino-ethylamino)-phenylamino]-2-propyl-benzo[de]isoquinoline-1,3-dione) were designed and synthsised based on naphthalimide. They were synthesized from o-bromonitrobenzene via three steps including SNArH, reductive and Buchwald-Hartwig reaction. Cu2+leads wavelength of S-1 blue shift, but Hg2+leads red shift. Both of metals make fluorescence quench. Probe S-2 has recognition of phenolic hydroxyl group. With the drippings of tyrosine, the fluorescence increased, the new peak in 595 nm was formed and both of the fluorescence increased in 517 nm and in 599 nm. S-2 has the presentation of a 1:1 S-2-tyrosine complex to recognise tyrosine through the formation of hydrogen bond of phenolic hydroxyl and N in o-phenylenediamine.