V. A. Kuksa et al. / Bioorg. Med. Chem. Lett. 10 (2000) 1265±1267
1267
Table 1. Growth inhibition of cultured cells derived from a variety of human tumours by oxa-spermidine derivatives/homologues
Panel of cell lines1a
Compound/Cytotoxicity [GI50 (mM)]b,c,d
1b
1c
1d
2a
2b
2c
2d
3
Leukaemia (6)
11.8
18.5
13.3
18.1
18.1
17.2
18.2
14.5
17.8
16.4
15.3
16.9
16.2
16.9
18.2
17.9
16.1
15.7
20.2
15.2
19.5
22.4
16.7
16.5
15.7
18.0
17.5
15.4
23.0
18.3
13.0
14.2
13.8
12.9
14.8
12.6
14.7
14.0
15.8
14.0
26.8
15.3
20.3
18.0
19.1
13.5
20.9
14.5
28.4
19.6
3.9
11.5
9.8
4.1
6.3
7.2
5.6
10.7
4.7
11.3
16.3
10.2
8.5
6.3
Non small cell lung cancer (9)
Colon cancer (7)
Cns cancer (6)
13.5
12.8
14.9
13.7
12.4
14.3
10.6
13.8
12.5
9.6
Melanoma (8)
10.9
12.7
16.5
16.1
10.0
11.2
Ovarian cancer (6)
Renal cancer (7)
Prostate cancer (2)
Breast cancer (7)
Mean valuee
aThe number of cell lines routinely tested is shown in parentheses.
bData obtained from NCI's in vitro tumour cells screen.
cData are mean values of the corresponding panel.
dThe value of each cell line (not shown) is an average of at least two testings.
eMean values over all cell lines tested.
sulphonamido group (i.e., Pmc) was used instead of the
Mts group in analogous oxa-polyamine homologues
(2a±d), the inhibitory activity of these novel compounds
showed a general increase. In contrast to the Mts deri-
vatives (1a±d), chain elongation in Pmc substituted oxa-
spermidine homologues led to a modest increase in
cytotoxicity. The introduction of a primary aminooxy
group (ONH2, 3) at the end of the alkyl chain of the
most active compound 2d showed no signi®cant change
in the cytotoxicity (Table 1).
versity for the ®nancial support, the centre of Mass
Spectrometry at the University of Wales, Swansea, for
mass spectroscopic analyses and the National Cancer
Institute (USA) for screening our compounds.
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Acknowledgements
The authors wish to thank NATO, The Royal Society
for a fellowship (to V.A.P.), The Robert Gordon Uni-