F. Dudouit et al. / Bioorg. Med. Chem. Lett. 10 (2000) 553±557
557
Figure 4. Eect of A, B and C on the relaxation of supercoiled plasmid DNA by topoisomerase I or II. The DNA (0.5 mg) was incubated with 4
units topoisomerase in the absence (lane TopI/II) or presence of drug at 10 or 50 mM. Etoposide (Etop.) and camptothecin (CPT) were used at 50
mM. Reactions were stopped with SDS and proteinase K. DNA samples were electrophoresed on agarose gel containing ethidium bromide. Nck,
nicked; Lin, linear; Rel, relaxed; Sc, supercoiled.
00
H5), 7.38 (d, J=8.37 Hz, 2, H3 ), 7.54 (s, 1, H3), 7.60 (d,
Acknowledgements
0
J=7.87 Hz, 2, H3 ), 7.74 (d, J=8.37 Hz, 2, H2 ), 8.00 (d,
00
0
J=7.87 Hz, 2, H2 ), 8.20 (sl, 2, NH2), 8.38 (sl, 2, NH2), 10.09
Supported by research grants (to C.B. and J.P.H.) from
the Ligue Nationale Francaise Contre le Cancer; (to
C.H. and P.C.) from the Actions de Recherches Con-
certees contract 95/00-193 and the FNRS, Televie 7/
4526/96. Support by the ``convention INSERM-CFB''
is acknowledged.
(s, 1, NH), 10.51 (s, 1, NH); MS (EI) for C27H27N5O2 (M+)
calcd 453, found 453. Anal. (C70.00H5.85N15.30O8.85) CHN.
10. Lee, M.; Coulter, D. M.; Lown, J. W. J. Org. Chem. 1988,
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van Galen, P. J. M.; Stiles, G. L.; Jacobson, K. A. J. Med.
Chem. 1994, 37, 636.
References and Notes
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9. A: mp >260 ꢀC; IR (KBr) 3500±3250, 1645, 1640, 1600; H
1
NMR (300 MHz; TFA) d 4.45 (sl, 2, CH2), 4.54 (sl, 2, CH2),
7.80 (m, 11, aromatics); MS (CI) for C20H21N5O2, 2H2O
(MH ) calcd 362, found 362. Anal. (C59.73H6.10N17.01O17.16
)
CHN. B: mp 185 ꢀC; IR (KBr) 3310, 1650, 1610; 1H NMR
(300 MHz; TFA) d 4.03 (s, 3, CH3), 4.46 (sl, 2, CH2), 4.54 (sl,
2, CH2), 7.56±06 (m, 10, aromatics); MS (EI) for C21H23N5O2,
2H2O (M+) calcd 377, found 377. Anal. (C61.25H6.41N16.75
O15.59) CHN. C: mp 99±101 ꢀC; IR (KBr) 3420, 3030, 1675,
1605; 1H NMR (300 MHz; TFA) d 3.92 (s, 2, CH2), 4.13 (s, 2,
CH2), 5.63 (sl, 2, CH2), 7.15±34 (m, 5, aromatics), 7.28 (s, 1,
24. Takebayashi, Y.; Pourquier, P.; Yoshida, A.; Kohlagen,
G.; Pommier, Y. Proc. Natl. Acad. Sci. USA 1999, 96, 7196.