Binuclear platinum (II)-terpyridine complexes. A new class of bifunctional DNA-intercalating agent.
A series of binuclear DNA-binding ligands was prepared by linking two (2,2':6',2"-terpyridine)platinum(II) moieties via alpha omega-dithiols of the type HS-[CH2]n-SH where n = 4-10. A monomeric analogue was also synthesized. Compounds were characterized by elemental analysis and electronic and n.m.r. spectroscopy. Viscometric measurements with sonicated rod-like DNA fragments and covalently closed circular DNA were performed to investigate the mode of binding of these agents. The ligands with n = 5 and 6 function as bis intercalators and form a single 'base-pair sandwich' in violation of neighbour-exclusion binding. Bifunctional reaction occurs for the ligand with n = 7, whereas the ligands with n = 8 and 10 show a preference for mixed monofunctional/bifunctional binding. The data do not permit definitive assignment of the binding mode of the ligands with n = 4 and 9. All compounds are growth-inhibitory against mouse leukaemia L1210 cells in culture with IC50 values in the range 2-14 microM.
D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004270:DNA, Circular / Q000187:drug effects; D007364:Intercalating Agents / Q000494:pharmacology; D008024:Ligands; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D013053:Spectrophotometry; D014783:Viscosity
D004270:DNA, Circular; D007364:Intercalating Agents; D008024:Ligands; D046911:Macromolecular Substances; D009944:Organoplatinum Compounds; D011725:Pyridines