I. Paterson et al. / Bioorg. Med. Chem. Lett. 17 (2007) 2443–2447
2447
Table 1. Cytotoxicity of dictyostatin (1), Taxol (2), discodermolide (3) and dictyostatin analogues 4, 5, 6 and 7 in cultured human cancer cells as
determined by MTT metabolism following 72-h exposure to the test agent
Compound
IC50/nMa
PANC-1 pancreatic
AsPC-1 pancreatic
DLD-1 colon
NCI/ADR Taxol-resistant
1
2
3
4
5
6
7
9.0 ( 5.6)
20 ( 23)
98 ( 34)
0.8 ( 3.8)
11 ( 1)
29 ( 8)
3.4 ( 0.2)
7 ( 2)
9.8 ( 1.5)
1000 ( 140)
160 ( 34)
59 ( 34)
130 ( 19)
1500 ( 140)
9.7 ( 1.8)
240 ( 2)
170 ( 19)
2100 ( 210)
31 ( 9.2)
410 ( 200)
85 ( 19)
790 ( 710)
2.4 ( 1.1)
150 ( 36)
1500 ( 460)
2100 ( 680)
8.2 ( 1.8)
1100 ( 230)
a Values are standard deviation (in parentheses) from a minimum of four separate experiments.
Zhu, G.; Edler, M. C.; Hamel, E.; Day, B. W.; Curran, D.
P. Org. Lett. 2005, 7, 2873; (c) Fukui, Y.; Bruckner, A. M.;
Acknowledgments
¨
Shin, Y.; Balachandran, R.; Day, B. W.; Curran, D. P.
Org. Lett. 2006, 8, 301; (d) Paterson, I.; Gardner, N. M.
Chem. Commun. 2007, 49.
NIH Grant No. CA-93455 provided financial support
for the biological assays and general project support
was provided by the EPSRC, AstraZeneca and the EC
(Marie Curie Fellowship to K.G.P.). We thank Dr. John
Leonard (AstraZeneca) for helpful discussions, Dr.
Richard Isbrucker and Dr. Pat Linley (HBOI) for assist-
ing in our biological evaluation and Dr. Stuart Mickel
(Novartis) for the gift of chemicals.
7. Gunasekera, S. P.; Gunasekera, M.; Longley, R. E. J. Org.
Chem. 1990, 55, 4912.
8. Review: Paterson, I.; Florence, G. J. Eur. J. Org. Chem.
2003, 2193.
9. (a) Hung, D. T.; Nerenburg, J. B.; Schreiber, S. L. J. Am.
Chem. Soc. 1996, 118, 11054; (b) Paterson, I.; Florence, G.
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Supplementary data
Supplementary data associated with this article can be
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