Synthesis, characterization and binding with DNA of four planaramineplatinum(II) complexes of the forms: trans-PtL2Cl2 and [PtL3Cl]Cl, where L = 3-hydroxypyridine, 4-hydroxypyridine and imidazo(1,2-alpha)pyridine.
Four new trans-planaramineplatinum(II) complexes, three of the form: trans-PtCl2L2, code named CH1, CH2 and CH4 where L = 3-hydroxypyridine, 4-hydroxypyridine and imidazo[1,2-alpha]pyridine, respectively, and one of the form: PtClL3, code named CH3 where L = 3-hydroxypyridine, have been prepared and characterized by elemental analyses and IR, Raman, mass and 1H NMR spectral studies. The interactions of the compounds with salmon sperm and pBR322 plasmid DNAs have been investigated and their activity against human ovarian cancer cell lines: A2780, A2780cisR and A2780ZD0473R have also been determined. The compounds are believed to form mainly monofunctional N7(G) and bifunctional intrastrand N7(G)N7(G) adducts with DNA, causing a local distortion of DNA as a result of which gel mobility of the DNA changes. The compound containing three planaramine ligands per molecule (CH3) is found to be less reactive than the compounds containing two planaramine ligands per molecule (CH1, CH2 and CH4), which in turn are less reactive than compounds containing one of the same planaramine ligands per molecule. The decrease in reactivity is reflected in lower molar conductivity values (indicating lower degree of dissociation), less pronounced changes caused to DNA conformation (indicating decreased level of platinum-DNA binding) and lower activity. The decreased reactivity of the compounds is due to a greater steric crowding produced by the bulky planaramine ligands. Changes in DNA conformation are also found to be a function of the actual nature of the planaramine ligand. The results illustrate structure-activity relationship.
Chowdhury
Mohammad Ashraf
MA
School of Biomedical Sciences, Cumberland Campus, C42, The University of Sydney, East Street, P.O. Box 170, Lidcombe, NSW 1825, Australia.
Huq
Fazlul
F
Abdullah
Ahmed
A
Beale
Philip
P
Fisher
Keith
K
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D018736:DNA Adducts / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry*
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D011725:Pyridines