摘要：A quantitative structure-activity relationship (QSAR) of a series of benzothiazole derivatives showing a potent and selective cytotoxicity against a tumorigenic cell line has been studied by using the density functional theory (DFT), molecular mechanics (MM+) and statistical methods, and the QSAR equation was established via a correlation analysis and a stepwise regression analysis. A new scheme determining outliers by “leave-one-out” (LOO) cross-validation coefficient (q n-i 2 ) was suggested and successfully used. In the established optimal equation (excluding two outliers), the steric parameter (MR R) and the net charge (Q FR) of the first atom of the substituent (R), as well as the square of hydrophobic parameter (IgP)2 of the whole molecule, are the main independent factors contributing to the anticancer activities of the compounds. The fitting correlation coefficient (R 2) and the cross-validation coefficient (q 2) values are 0.883 and 0.797, respectively. it indicates that this model has a significantly statistical quality and an excellent prediction ability. Based on the QSAR studies, 4 new compounds with high predicted anticancer activities have been theoretically designed and they are expected to be confirmed experimentally.

摘要：As a group of diversified frameworks, quinazolin derivatives displayed a broad field of biological functions, especially as anticancer. To investigate the quantitative structure-activity relationship, 3D-QSAR models were generated with 24 quinazolin scaffold molecules. The experimental and predicted pIC50 values for both training and test set compounds showed good correlation, which proved the robustness and reliability of the generated QSAR models. The most effective CoMFA and CoMSIA were obtained with correlation coefficient2ncv r of 1.00 （both） and leave-one-out coefficient q2 of 0.61 and 0.59, respectively. The predictive abilities of CoMFA and CoMSIA were quite good with the predictive correlation coefficients （2pred r ） of 0.97 and 0.91. In addition, the statis-tic results of CoMFA and CoMSIA were used to design new quinazolin molecules.

摘要：A novel ligand-based pharmacophore model for KDR kinase was generated on the basis of chemical features of 30 KDR kinase inhibitors. This pharmacophore model consists of one hydrogen-bond acceptor, one hydrogen-bond donor and two hydrophobic groups. Several methods have been used to validate the model, suggesting that it can serve as a reliable tool for virtual screening to facilitate the discovery of novel KDR inhibitors. The model was then used as database search query from the National Cancer Institute （NCI） database for the rational design to identify new hit compound.

摘要：A series of new hybrids of dehydroandrographolide(TAD),a biologically active natural product,bearing nitric oxide(NO)-releasing moieties were synthesized and designated as NO-donor *** biological activities of target compounds were studied in human erythroleukemia K562 cells and breast cancer MCF-7 *** evaluation indicated that the most active compound I-5 produced high levels of NO and inhibited the proliferation of K562(IC_(50) 1.55μmol?L^(–1))and MCF-7(IC_(50)2.91μmol?L^(–1))cells,which were more potent than the lead compound TAD and attenuated by an NO *** conclusion,I-5 is a novel hybrid with potent antitumor activity and may become a promising candidate for future intensive study.

摘要：A hybrid pharmacophore approach was used to design and synthesize a series of coumarin derivatives bearing 2-methylbiphenyl moiety, which were evaluated for their in vitro anticancer activities against four cancer cell lines(MCF-75 A549, H460 and HT29) and PD-1/PD-L1 inhibitory activities. Moreover, several compounds with excellent anticancer activities were selected to evaluate the cytotoxicities against one normal cell line(HEK-293). The most promising compound llo showed the best anticancer activities against the four tested cancer cell lines with the IC50 values of 6.45, 8.65, 6,57 and 8.13 gmol/L, respectively, and displayed weak cytotoxicity on the normal cell(HEK-293). Furthermore, screening of PD-1 /PD-L1 inhibitory activity revealed that compound llo could effectively inhibit the binding of PD-1/PD-L1, and the binding interactions of compound llo with PD-L1 protein were explored by molecular docking. All above evidences showed that compound llo might be worthy of further study as a valuable leading compound for the treatment of cancer.

摘要：Zinc binding group(ZBG)is the crucial moiety in the chemical structure of any HDAC *** the present study,a series of sulphur-containing ZBG were designed and synthesized in the novel HDAC inhibitors to replace the classical ZBGs of SAHA and BML-210,hydroxamic acids and benzamides,*** HDAC inhibitory activity and the structure-activity relationships of these molecules were analyzed.A sulphur-rich group,diethylcarbamo(dithioperoxo)thioate,was finally identified as a novel potent *** all the synthesized compounds,4 d was much more potent compared with BML-210,and it showed similar inhibitory effect of SAHA against HDAC isoforms 1 and ***,it was chosen as a lead compound.

摘要：Starting from 4,6-dimethyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-aminopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, amide derivatives 7a-h, pyridopyra- zolopy-rimidine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative compounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that some of the synthesized compounds showed remarkable anticancer activities, especially 8b which displayed the highest activity among the tested compounds with IC50 equal to 2.9, 2.6 and 2.3 μmol. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent compound 8b using struc- ture-based modeling tools.

摘要：To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro anticancer activities were evaluated. The four peptide cycloacetal derivatives did not showed any activities, which demonstrated that this kind of cycloacetal derivatives might be suitable as prodrugs. The two peptide heterocycle compounds were found to show obvious activities at both enzyme and cell levels. These results provide us a new clue for the modification of peptide aldehyde proteasome inhibitors.