3506 J ournal of Medicinal Chemistry, 2003, Vol. 46, No. 16
Zhang et al.
precipitate was formed when the mixture was cooled to room
temperature, which was then collected by filtration. Single
crystals of complexes II and III were both obtained by slow
evaporation of the solvent of acetone and water. It is interest-
ing to note that I or II can also be synthesized by the reaction
of ligand L1 or L2 with K2PtCl4 in a mixture of acetone and
water, during which the Boc group is cleaved, as shown by 1H
NMR spectra and X-ray crystal analysis. However, L3 does not
undergo the same cleavage reaction during the preparation
of complex III. Elemental anal. found (calculated) for complex
I (%): C, 29.0 (29.4); H, 2.63 (2.68); N, 9.39 (9.36). 1H NMR of
complex I in DMSO-d6 (ppm): δ 8.99 (d, 1H), 8.68 (d, 1H), 8.58
(d, 1H), 7.69 (m, 1H), 7.57 (t, 1H), 7.50 (d, 1H), 6.00 (s, 2H).
Elemental anal. found (calculated) for complex II (%): C, 30.8
10 mmol‚mL-1 Tris (pH 10.5) prior to reading plates. The OD
value was read on a plate reader at a wavelength of 515 nm.
Media and DMSO control wells, in which complexes were
absent, were included in all the experiments. The percent
growth inhibitory rate of treated cells was calculated by
(ODcontrol - ODtest)/ODcontrol × 100. Results of complexes were
expressed as IC50 (the drug concentration that reduces by 50%
the absorbance in treated cells with respect to untreated cells)
that was calculated by the Logit method. Finally, the mean
IC50 was calculated using the data from three replicate tests.
Note. Crystallographic data of complexes II and III have
been deposited at the Cambridge Crystallographic Data Cen-
tre, CCDC Nos. 192536 and 192537. Any queries relating to
the data can be e-mailed to deposit@ccdc.cam.ac.uk.
1
(31.1); H, 3.00 (3.03); N, 9.13 (9.08). H NMR of complex II in
DMSO-d6 (ppm): δ 9.01 (d, 1H), 8.67 (d, 1H), 8.60 (d, 1H), 7.70
(m, 1H), 7.57 (t, 1H), 7.50 (d, 1H), 3.81 (q, 1H), 1.33 (d, 3H).
Elemental anal. found (calculated) for complex III (%): C, 32.0
(32.2); H, 3.40 (3.44); N, 8.07 (8.04). Two sets of 1H NMR
resonances for complex III in CDCl3 (ppm), set 1: δ 9.365 (d,
1H), 8.735 (d, 1H), 8.426 (t, 1H), 8.638 (m, 1H), 7.572 (m, 1H),
7.495 (m, 1H), 6.002 (m, 1H), 3.425 (m, 1H), 3.065 (m, 2H),
2.857 (s, 3H), 2.305 (m, 2H), 1.481 (s, 9H). For set 2: δ 9.300
(d, 1H), 8.645 (d, 1H), 8.426 (t, 1H), 8.638 (m, 1H), 7.572 (m,
1H), 7.495 (m, 1H), 6.656 (m, 1H), 3.114 (m, 1H), 2.620 (m,
2H), 2.761 (s, 3H), 2.171 (m, 2H), 1.481 (s, 9H).
Ack n ow led gm en t. We are thankful for the financial
support from the National Natural Science Foundation
of China (Grant Nos. 29925102, 20231010, and 20228102)
and the Ministry of Education for Specialized Research
Fund for the Doctoral Program of Higher Education
(Grant No. 20010284029). The authors thank Chenghui
Xu and Weiyi Yang for cytotoxicity assays.
Refer en ces
Rea ction of Com p lexes w ith 5′-GMP . Platinum(II) com-
plex I (II or III) (0.05 mmol) was dissolved in a mixture of
DMF and water, and an aqueous solution of 5′-GMP (0.05
mmol) was added with stirring. The reaction was continued
for about 48 h at room temperature, and then the solvent was
removed. ESMS spectra were recorded for the resulting
product.
Cytotoxicity Assa ys. Cytotoxicity assays of platinum
complexes are performed on a diverse panel of human tumor
cell lines. Tumor cell lines were grown in RPMI-1640 medium
supplemented with 10% (v/v) heat-inactivated fetal bovine
serum, 2 mmol/L glutamine, 100 U/mL penicillin, and 100 µg/
mL streptomycin in a highly humidified atmosphere of 95%
air with 5% CO2 at 37 °C.
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