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7.
Studies on Synthesis, Activity and Binding with DNA
of {TRANS-PDCL(NH3)2}[{TRANS-PD(2-HYDROXYPYRIDINE)}2{H2N(CH2)6NH2}2]2CL4,
[{TRANS-PDCL(C5H5NO)2}2
{m-TRANS-PD(NH3)}2{(NH2(CH2)6NH2)2}]CL4
AND {TRANS-PDCL(NH3)2}[{TRANS-PD(4-HYDROXYPYRIDINE)}2{H2N(CH2)6NH2}2]2CL4
Fazlul Huq*1, Mohammad Farhad1, Jun Qing Yu1,
Philip Beale2 and Keith Fisher3
1 Discipline of Biomedical Sciences, Cumberland Campus,
C42, The University of Sydney, East Street, PO Box 170, Lidcombe,
NSW 1825, Australia.
2 Sydney Cancer Centre, Concord Repatriation General
Hospital, Concord, NSW, Australia.
3 School of Chemistry, The University of Sydney, NSW
2006, Australia.
Correspondence should be made to Fazlul Huq,
Fazlul.Huq@sydney.edu.au
Abstract:
This paper describes the synthesis, characterization,
cytotoxicity of three trinuclear Pd-Pd-Pd complexes code named
MH6, MH7 and MH8 containing respectively two 2-hydroxypyridine,
3-hydroxypyridine and 4-hydroxypyridine ligands bound to each of
the terminal metal ions. In addition to activity against human
ovarian cancer cell lines: A2780, A2780cisR and
A2780ZD0473R, cell uptake, DNA-binding and nature of interaction
of the compounds with pBR322 plasmid DNA have also been
determined. Although the three compounds are found to be less
active than cisplatin against all the three cell lines,
reduction in their activity in going from parent cell line A2780
to the two resistant cell lines is much less. MH6, the most
active compound among MH6, MH7 and MH8, is in fact more active
against the resistant cell line A2780cisR than the
parent cell line A2780. In MH6, each of the two terminal
palladium ions is bound to two 2-hydroxypyridine ligands whereas
in MH7 and MH8, the ligands present are 3-hydroxypyridine and 4-hydroxypyridine.
MH6, MHAs MH6, MH7 and MH8 are all expected to bind with DNA
forming mainly interstrand GG adducts, the variation in activity
among them is believed to be associated with non-covalent
interactions such as hydrogen-bonding, steric hindrance and
stacking interaction. The results can be seen to illustrate
structure-activity relationships.
KEYWORDS: Cisplatin; BBR3464; Palladium; 2-Hydroxypyridine;
3-hydroxypyridine; 4-hydroxypyridine; Ovarian cancer; MTT.
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