4454
W.-J. Cho et al. / Bioorg. Med. Chem. Lett. 13 (2003) 4451–4454
Figure 3. Hypothetical docking model of 7d with topoisomerase I–DNA complex.
Pommier, Y.; Staker, L. S.; Cushman, M. J. Med. Chem. 2003,
site due to the lacks of the length of chain to reach the
protein functional group.
46, 3275.
7. Yamashita, Y.; Fujii, N.; Murakaya, C.; Ashizawa, T.;
Okabe, M.; Nakano, H. Biochemistry 1992, 31, 12069.
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In summary, amine substituents at the C-1 position of
3-arylisoquinolines provide novel, potent and water
soluble top I inhibitors with significant antitumor cyto-
toxicity. The selective cytotoxicity of 9b against doxo-
rubicin- and daunorubicin-resistant tumor cells is highly
significant. Finally, these compounds represent a pro-
mising new class of non-camptothecin top I inhibitors
worthy of a further study.
10. Redinbo, M. R.; Stewart, L.; Kuhn, P.; Champoux, J. J.;
Hol, W. G. J. Science 1998, 279, 1504.
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Acknowledgements
12. Cho, W.-J.; Kim, E.-K.; Park, I. Y.; Jeong, E. Y.; Kim,
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The financial support from Korea Research Foundation
(KRF-2002-015-EP0142) of Korea is appreciated.
14. Kim, K. E.; Cho, W.-J.; Chang, S. J.; Yong, C. S.; Lee,
C. H.; Kim, D. D. Int. J. Pharm. 2001, 217, 101.
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19. 500 ng supercoiled pBR 322 DNA was incubated with 1
unit topoisomerase I in the absence or presence of camp-
tothecin or the compounds for 30 min at 37 ꢀC. The reaction
mixtures were analyzed on 1% agarose gel followed by ethi-
dium bromide staining.