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F.A. Beckford et al. / Inorganic Chemistry Communications 12 (2009) 1094–1098
References
[1] D.L. Klayman, J.P. Scovill, J.F. Bartosevich, J. Bruce, J. Med. Chem. 26 (1983)
39.
[2] D. Kovala-Demertzi, M.A. Demertzis, J.R. Miller, C. Papadopoulou, C. Dodorou,
G. Filousis, J. Inorg. Biochem. 86 (2001) 555.
[3] J. Garcia-Tojal, A. Garcia-Orad, J.L. Serra, J.L. Pizarro, L. Lezamma, M.I. Arriortua,
T. Rojo, J. Inorg. Biochem. 75 (1999) 45.
[4] D.H. Petering, Bioinorg. Chem. 1 (1972) 255.
[5] (a) G. Chu, J. Biol. Chem. 269 (1994) 787–790;
(b) M.A. Fuertes, C. Alonso, J.M. Perez, Chem. Rev. 103 (2003) 645–662;
(c) R. Agarwal, S.B. Kaye, Nat. Rev. Cancer 3 (2003) 502–516.
[6] G. Sava, A. Bergamo, Int. J. Oncol. 17 (2000) 353–365.
[7] J.M. Rademaker-Lakhai, D. Van den Bongard, D. Pluim, J.H. Beijnen, J.H.
Schellens, Clin. Cancer Res. 10 (2004) 3717–3727.
[8] (a) G. Sava, R. Gagliardi, A. Bergamo, E. Alessio, G. Mestroni, Anticancer Res. 19
(1999) 969–972;
Fig. 4. Effect of the increasing amount of 1 on the relative viscosity of ct-DNA at 306
( 0.1) K; [DNA] = 0.1 mM.
(b) A. Bergamo, B. Gava, E. Alessio, G. Mestroni, B. Serli, M. Cocchieto, S. Zorzet,
G. Sava, Int. J. Oncol. 21 (2002) 1331–1338;
(c) M. Groessl, E. Reisner, C.G. Hartinger, R. Eichinger, O. Semenova, A.R.
Timerbaev, M.A. Jakupec, V.B. Arion, B.K. Keppler, J. Med. Chem. 50 (2007)
2185–2193.
Table 3
Antiproliferative activity of complexes 1–3 in panel of four human cancer cell lines.
[9] (a) C.G. Hartinger, S. Zorbas-Seifried, M.A. Jakupec, B. Kynast, H. Zorbas, B.K.
Keppler, J. Inorg. Biochem. 100 (2006) 894–904;
Compound
IC50 (l
M)a
(b) S. Kapitza, M. Pongratz, M.A. Jakupec, P. Heffeter, W. Berger, L. Lackinger,
B.K. Keppler, B. Marian, J. Cancer Res. Clin. Oncol. 131 (2005) 101–110;
(c) B.K. Keppler, M. Henn, U.M. Juhl, M.R. Berger, R. Niebl, F.E. Wagner, Prog.
Clin. Biochem. Med. 10 (1989) 41–69;
MDA-MB-231
MCF-7
HCT 116
HT-29
1
2
3
5.04 0.99
2.67 0.38
9.01 3.52
730
39.2 8.1
13.2 0.25
18.05 11.8
506 86
9.34 1.08
3.27 0.40
12.3 0.06
3.10
8.32 3.08
4.94 0.50
17.4 6.39
24.3
(d) M. Pongratz, P. Schluga, M.A. Jakupec, V.B. Arion, C.G. Hartinger, G.
Allmaier, B.K. Keppler, J. Anal. At. Spectrom. 19 (2004) 46–51.
[10] E.D. Kreuser, B.K. Keppler, W.E. Berdel, A. Piest, E. Thiel, Semin. Oncol. 19
(1992) 73–81.
[11] R.E. Morris, R.E. Aird, P. Murdoch del, S.H. Chen, J. Cummings, N.D. Hughes, S.
Parsons, A. Parkin, G. Boyd, D.I. Jodrell, P.J. Sadler, J. Med. Chem. 44 (2001)
3616–3621.
Cisplatin
a
50% inhibitory concentration after exposure for 72 h in the MTS assay. Values
are means standard deviations.
[12] O. Novakova, J. Kasparkova, V. Bursova, C. Hofr, M. Vojtiskova, H. Chen, P.J.
Sadler, V. Brabec, Chem. Biol. 12 (2005) 121–129.
[13] R.E. Aird, J. Cummings, A.A. Ritchie, M. Muir, R.E. Morris, H. Chen, P.J. Sadler,
D.I. Jodrell, Br. J. Cancer 86 (2002) 1652–1657.
[14] S.M. Guichard, R. Else, E. Reid, B. Zeitlin, R. Aird, M. Muir, M. Dodds, H. Fiebig,
P.J. Sadler, D.I. Jodrell, Biochem. Pharmacol. 71 (2006) 408–415.
[15] M.A. Bennett, A.K. Smith, Dalton Trans. (1974) 233.
[16] F.A. Beckford, A. Holt, J. Undergraduate Chem. Res. 6 (2007) 173. Briefly,
equimolar amounts of 9-anthraldehyde and the appropriate N4 alkyl-
substituted thiosemicarbazide were suspended in anhydrous ethanol
(MTS assay) which measures mitochondrial dehydrogenase activ-
ity as an indication of cell viability. The effects of the compounds
on the viability of these cells were evaluated after an exposure per-
iod of 72 h. All the complexes showed moderate cytotoxic poten-
cies and their IC50 values, corresponding to inhibition of cancer
cell growth at the 50% level, are listed in Table 3. As a general
observation, complex 2 is the most active against all the cell lines.
Also the alkyl group on N(3) is non-innocent as there appears to be
an decrease in potency as the alkyl group gets bigger. Between cell
lines there is also another clearly discernible trend in that the com-
pounds showed higher activities against the MDA-MB-231 cells,
which are estrogen receptor negative (ER(-)) vs. the ER(+) MCF-7
cells. There is a similar trend present in the colon cell lines – activ-
ity is higher in the HCT-116 cells which normally does not express
cyclooxygenase COX-2.
containing
a few drops of glacial acetic acid. The reaction mixture was
heated at reflux for 3½ h and after cooling the light precipitate that formed
was collected by filtration and washed thoroughly with ethanol followed by
ether and dried in the vacuum.
[17] I. Moldes, E. de la Encarnación, J. Roo, Á. Alvarez-Larena, J.F. Pinella, J.
Organomet. Chem. 566 (1998) 165.
[18] C.G. Hamaker, D.P. Halbach, J. Organomet. Chem. 691 (2006) 3349.
[19] H. Beraldo, W.F. Nacif, L.R. Teixeria, J.S. Reboucas, Transition Met. Chem. 27
(2002) 85.
[20] D.X. West, J.K. Swearigen, J. Valdee-Martinez, S. Hernandez-Ortegs, A.K. El-
Sawaf, F. van Meurs, A. Castineiras, I. Garcia, E. Bermejo, Polyhedron 18 (1999)
2919.
[21] C.G. Hamaker, D.P. Halbach, Polyhedron 28 (2009) 2228.
[22] F.A. Allen, Acta Crystallogr. Sect. B 58 (2002) 380.
[23] O. Novakova, H. Chen, O. Vrana, A. Rodger, P.J. Sadler, V. Brabec, Biochemistry
42 (2003) 11544.
Acknowledgements
The project described was supported by NIH Grant No. P20 RR-
16460 from the IDeA Networks of Biomedical Research Excellence
(INBRE) Program of the National Center of Research Resources.
[24] J.R. Lacowicz, Principles of Fluorescence Spectroscopy, 3rd ed., Springer, New
York, 2006.
[25] K.S. Ghosh, B.K. Sahoo, D. Jana, S. Dasgupta, J. Inorg. Biochem. 102 (2008)
1711.
[26] E.C. Long, J.K. Barton, Acc. Chem. Res. 23 (1990) 271–273.
[27] G. Cohen, H. Eisenberg, Biopolymers 8 (1969) 45–55.
Appendix A. Supplementary material
CCDC 733807 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The