2-chloro-4-nitro-1-((Trifluoromethyl)sulfi Nyl)Benzene:synthesis And Anti-cancer Studies

N-phenyl-2,2-dichloroacetamide analogues are potential anti-cancer agents whosetarget is pyruvate dehydrogenase kinase(PDK). Our earlier researchesshow that whensynthesizing N-phenyl-2,2-dichloroacetamide, a new compound,2-chloro-4-nitro-((trifluoromethyl)sulfinyl)benzene was found, which might have a even higheranti-cancer activity. Based on this compound, the following issueswere studied.1,2-chloro-4-nitro-((trifluoromethyl)sulfinyl) benzene analogues: synthesis andanti-cancer studiesAt first, a series of2-chloro-4-nitro-((trifluoromethyl)sulfinyl) benzene analogueswere synthesized, and the biological activity tests of which shown that anymodifications with nitro group or sulfinyl group might result in the loss of theiranti-cancer activity. However, modification with halogen atoms had little effect on theanti-cancer activity of2-halo-4-nitro-((trifluoromethyl)sulfinyl)benzene. Theanti-cancer activity of2-chloro-4-nitro-((trifluoromethyl)sulfinyl)benzene was thehighest among all the compounds synthesized. Next, the anti-cancer behavior wasstudied based on16kinds of cancer cell lines. The results showed that2-chloro-4-nitro-((trifluoromethyl)sulfinyl)benzene had good inhibitions onall thesecell lines, especiallyfor K562cell linewhoseIC50is89.3nM. At last, monocyte proliferation assay showedthat under a concentration of0.12uM,2-chloro-4-nitro-((trifluoromethyl)sulfinyl)benzene had little effects on monocyte proliferation. It can be concluded that2-chloro-4-nitro-((trifluoromethyl)sulfinyl)benzene didn’t negatively affect the immunesystem.2, Design and synthesis of small molecule probe:In order to identify the target, a small molecule probe was designed. Taking intoaccount that2-chloro-4-nitro-((trifluoromethyl)sulfinyl)benzene contains sulfur, aradioactive sulfur isotope S-35is selected as the label group. Two routes were applied tosynthesize2-chloro-4-nitro-((trifluoromethyl)sulfinyl)benzene, one of which introducedsulfur to the compound. Studies on structure-activity implyed that nitro group andsulfinyl group were the pharmacophores, and the anti-cancer activity of2-halo-4-nitro- ((trifluoromethyl)sulfinyl)benzene didn’t vary significantly with modification ofhalogen atoms. Therefore, the azido photoaffinity group was designed to replacechlorine group. With the reaction between2-chloro-4-nitro-((trifluoromethyl)sulfinyl)benzene and sodium azide, an azide compound were synthesized. Althoughvarious mass spectrometry methods had been employed, the molecular weight of theproduct was difficult to determine. A new approach was provided, where the unstablearyl azide compound were cultured as single crystal under conditions of lowtemperature and light. The single-crystal X-ray diffraction analysis implied that thecompound was1-azido-2-chloro-4-nitrobenzene. That is, trifluoromethyl sulfinyl groupwas substituted by azide group, rather than chlorine group. It can be concluded that thehalogen group on2-halo-4-nitro-((trifluoromethyl)sulfinyl)benzene is difficult to bereplaced with chlorine group. Therefore the azide compounds are expected to besynthesized from aromatic compound with Hydrazine group and N2O4.