Discovery of a series of pyridopyrimidine derivatives as potential topoisomerase I inhibitors |
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| Authors: | Jun-PengZhang ;Jie Huang ;Chao Liu ;Xu-Fang Lu ;Bao-Xiang Wu ;Li Zhao ;Na Lu ;Qing-Long Guo ;Zhi-Yu Li ;Cheng Jiang |
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| Affiliation: | a Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;
b Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;
c Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China;
d Gansu Institute for Food and Drug Control, Lanzhou 730070, China |
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| Abstract: | A series of new 3-benzoheterocyclic substituted pyridopyrimidines were designed and synthesized. Structures of the compounds were determined by IR, 1H NMR, and elemental analyses. The antiproliferation activity of 13 novel compounds was evaluated in A549, HL-60, BGC-823 and SMMC-7721 cell lines. Compounds 3, 5, 7, 8, 9, 10 showed potent inhibitory activity against the four tested cancer cell lines. These six compounds were examined for Top I inhibition at 100 mmol/L by measuring the relaxation of supercoiled DNA in plasmid pBR322. Most of the tested compounds inhibited the enzyme at this concentration. The most potent compound 9 was as potent as camptothecin. |
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| Keywords: | Topoisomerase I inhibitors Pyridopyrimidine Anticancer Synthesis |
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