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

摘要

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, A2780~(cisR)and A2780~(ZD0473R), 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 A2780~(cisR) 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.