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Quinazoline compounds researchers in recent years much attention to a class of heterocyclic compounds, and are found on the NF-κB signaling pathway inhibition. In the first part of the work, by selecting a series of research literature quinazoline derivative, such compounds have proven to be the activation of NF-κB inhibition, therefore, these compounds are based on NF-κB as a target play role in the experiment using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of this series of compounds for three-dimensional quantitative structure activity relationship (3D-QSAR) studies, the establishment of the 3D-QSAR CoMFA and CoMSIA models. Calculate its cross-validation correlation coefficient q 2 , respectively, 0.823 and 0.795; non-cross-validated correlation coefficient R 2 , respectively 0.979 and 0.980; standard error of 0.149 and 0.144, respectively SEE , indicating that the model is reasonable, credible, and has good predictive ability. QSAR analysis showed that: (1) the substituent R 3 bits (see Table 2.1, the same below) the introduction of a large volume of positively charged hydrogen bond acceptor groups to improve the activity of beneficial compounds; ( 2) the substituent R 5 , R 6 bits should introduce negatively charged groups, to avoid introducing a hydrophobic group; and R 6 bits into hydrogen bond donor group on the activity of compounds beneficial; (3) substituents R 7 bit into a small volume groups favor increased activity of the compounds; (4) R 4 substituent volume size, electronegativity little weak activity of the compound; (5) hydrogen bond donor group not significantly reduce the biological activity of the compounds. Application of these rules to guide quinazoline inhibitor of NF-κB design and structural optimization, in order to find the ideal anti-tumor compounds provide an important basis. Imidazo [1,2-a] pyridine anticancer activity due to its good structure is widely used in medicines, in the second part of the work, for Organic Chemistry, State Key Laboratory of synthetic series of novel imidazo [ 1,2-a] pyridine derivatives (TIP) for anti-tumor activity. Select the human cervical carcinoma cell line HeLa and human acute monocytic leukemia cell line THP-1 cell line was tested with different concentrations (0,40,80,160,320,640 μM) of compounds TIP process them, 48 h, measured significant changes in cell proliferation, prove this series TIP compounds on HeLa and THP-1 cell proliferation inhibition, and this inhibition of proliferation in a dose dependent manner. For HeLa cells, TIP-06, 14 Compound No. IC 50 and 54.80 respectively of 46.96μM, the TIP-08, 13 do not have significant cytotoxic activity; for THP-1 cells, TIP-02, 06 and 08 on compound No. IC 50 , respectively, the 53.01,36.81,27.37 μM, compound TIP-10, 14 do not have significant cytotoxic activity; description, HeLa and THP-1 cells For this series of compounds TIP strain sensitivity of different cell lines tested for a certain selectivity of these compounds, and this inhibition selectivity and structure of the compound has a lot on structure-activity relationships of these compounds will be studied TIP derivatives in the post to get more research.
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