Synthesis,Characterization And Properties Of Novel Carbazole-based Schiff Base/Acylhydrazone Derivatives

In recent years,detection for metal ions and anions by colorimetric and fluorescent chemosensors is gradually becoming a new hotspot in the fields of environmental monitoring and biological science because these chemosensors have many advantages such as highsensitivity,selectivity and easy of fabrication.In addition,a large number of studies have also shown that highly efficient and specific cell division cycle 25 B phosphatase(Cdc25B)inhibitors will provide new tools and means for targeting cancer therapy,and protein tyrosine phosphatase 1B(PTP1B)has become a potential target for the treatment of type II diabetes and obesity.Therefore,the synthesis and development of highly selective and powerful Cdc25 B and PTP1 B inhibitors are important for the treatment of cancer,diabetes and obesity.Carbazole molecule has been favored by scientists in the field of ion recognition and medicine,which has the properties of a large conjugation systerm and strong intramolecular electron transfer,and is an important pharmacophore in medicine.In this paper,a series of novel Schiff base and acylhydrazone derivatives based on carbazole skeleton were designed and synthesized,and its spectral properties,ion recognition mechanism and inhibitory activity on Cdc25 B and PTP1 B have been researched.The results are as follows:1.In this papre,twenty five novel target compounds were designed and synthesized,including eleven new carbazole Schiff base derivatives based on diaminoglutaronitrile LI-L1~L6 and LII-L1~L5,four new carbazole Schiff base derivatives based on 1,3-diaminoguanidine hydrochloride LIII-L1~L4 and ten new carbazole-benzimidazole acylhydrazone derivatives LIV-L1~L10.Their structures were characterized by spectroscopic techniques,X-ray single crystal diffraction and elemental analysis.2.The 1H and 13 C NMR signals of representative target compounds LIII-L4 and LIV-L3 were assigned by the 1H NMR,13 C NMR,2D NMR(including 1H-1H COSY,HMBC,HSQC)and variable-temperature 1H NMR spectra.3.The ion recognition ability of the target compounds LI~LIV were investigated.The inhibitory activity of the target compounds LIV against Cdc25 B and PTP1 B were evaluated.The experimental results are as follows:(1)The target compounds LI-L1~L6 and LII-L1~L5 have the property of high selectivity naked eye,UV-vis and fluorescence “turn-on” recognition of Cu2+ in CH3 CN.These compounds can be used as the probes for detection of Cu2+ in environmental water.(2)The target compound LIII-L1 has the properties of high selectivity naked eye,UV-vis and fluorescence “turn-off” recognition of Ac O-and F-in CH3 CN.The target compounds LIII-L1~L4 have potential application value for the detection of Ac O-in marine sediments and the content of F-in drinking water.(3)The target compound LIV-L3 has the property of high selectivity fluorescence quenching to identify Cu2+ and Fe3+ in CH3 CN.The target compounds LIV-L1~L10 have potential application value for the detection of Cu2+ and Fe3+ in biological and environmental water.The target compounds LIV-L1~L10 have high inhibitory activity against Cdc25 B and PTP1 B.Among them,the inhibitory activity of compounds LIV-L4 and LIV-L8 against PTP1 B are higher than that of the positive control drug oleanolic acid.It is noteworthy that the target compound LIV-L4 has potent inhibitory activity against Cdc25 B and PTP1 B.The target compounds LIV-L1~L10 have potential application value in anticancer and antidiabetic.4.The obtained research results in this paper will provide important basis for the development of novel cation and anion recognition receptors,novel Cdc25 B and PTP1 B inhibitors.The research of this thesis is of great significance.