摘要
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 anti- proliferation 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 μmol/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.
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 anti- proliferation 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 μmol/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.
基金
supported by the National Natural Science Foundation of China(No.21072232)
the Fundamental Research Funds for the Central Universities(No.JKZ2011002)
the National Science&Technology Major Project(Nos.2012ZX09304-001 and 2013ZX09103-001-007)
the Program for Changjiang Scholars and Innovative Research Team in University(No.PCSIRT-IRT1193)
the‘‘Qinglan Project’’of Jiangsu Province
