3774
C. P ꢀe rez-Melero et al. / Bioorg. Med. Chem. Lett. 14 (2004) 3771–3774
Figure 2. Inhibition of tubulin polymerization (as microtubule protein, MTP) by compounds 1a–7a, CS A-4 and naphthylcombretastatin, expressed
as percentage of polymerization for noninhibited protein. MTP concentration is 1.5 mg/mL.
analogues with activities that do not fit into the SAR for
these type of compounds.
8. Nandy, P.; Banerjee, S.; Gao, H.; Hui, M. B.; Lien, E. J.
Pharm. Res. 1991, 8, 776.
9
. Brown, M. L.; Rieger, J. M.; Macdonald, T. L. Bioorg.
Med. Chem. 2000, 8, 1433, and references cited therein.
1
1
1
0. Maya, A. B. S.; del Rey, B.; Pel ꢀa ez Lamami ꢀe de Clairac,
R.; Caballero, E.; Barasoain, I.; Andreu, J. M.; Medarde,
M. Bioorg. Med. Chem. Lett. 2000, 10, 2549.
1. Maya, A. B. S.; P ꢀe rez-Melero, C.; Mateo, C.; Alonso, D.;
Fern ꢀa ndez, J. L.; Pel ꢀa ez, R.; Caballero, E.; Medarde, M.
J. Med. Chem., in press.
Acknowledgements
Financial support came from Spanish DGI-MCyT
PPQ2001-1977), Junta de Castilla y Le oꢀ n (SA073/02)
(
2. Plobek, N.; Delorme, D.; Wei, Z.-Y.; Yang, H.; Zhou, F.;
Schwarz, P.; Gawell, L.; Gagnon, H., et al. J. Med. Chem.
and european FEDER funds. A. B. S. Maya thanks
Universidad de Salamanca for a predoctoral grant.
Cytotoxicity assays were performed by Instituto Biomar
S. A. (Le oꢀ n, Spain). The authors are grateful to CIDTA
for the use of their equipment.
2
000, 43, 3878.
3. Deady, L. W.; Desneves, J.; Ross, A. C. Tetrahedron 1993,
9, 9823.
1
1
4
4. For the determination of aqueous solubility, samples
were shaken in 10 mM phosphate buffer, pH 7.0, at room
temperature for 72 h. Next, they were filtered and their
absorbance in the UV–vis was measured. Solubility: mg/
mL is 1a: 0.04, 3a: 0.07, 4a: 0.03, 5a: 0.04, 7a: 0.01,
naphthylcombretastatin: 0.01 and CS A-4: 0.05. (The
value reported in the literature for CS A-4 is 0.11 mg/mL
in PBS; Ohsumi, K.; Hatanaka, T.; Nakagawa, R.;
Fukuda, Y.; Morinaga, Y.; Suga, Y.; Nihei, Y.; Ohishi,
K.; Akiyama, Y.; Tsuji, T. Anticancer Drug Des. 1999, 14,
539).
15. San Feliciano, A.; Medarde, M.; Pel ꢀa ez Lamami ꢀe de
Clairac, R.; L oꢀ pez, J. L.; Puebla, P.; Gr ꢀa valos, M. D. G.;
Ruiz, P.; Garc ꢀı a de Quesada, M. T. Arch. Pharm.
(Weinheim) 1993, 326, 421.
16. Dumortier, C.; Gorbunoff, M.; Andreu, J. M.; Enge-
lborghs, Y. Biochemistry 1996, 35, 4378–4395.
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