Synthesis and biological evaluation of platinum–acridine hybrid agents modified with bipyridine non-leaving groups

The use of 2,2′-bipyridines (4,4′-R₂-2,2′-bpy; R = H, Me, OMe, CF₃) as non-leaving groups (L–L) in platinum–acridinylthiourea conjugates, PtCl(L-L)(ACRAMTU)](NO₃)₂, has been investigated. All bpy-substituted complexes (2–5) show micromolar activity in HL-60 (leukemia) and H460 (lung) cancer cell lines but proved to be significantly less potent than the prototypical compound (1) containing aliphatic ethane-1,2-diamine. NMR and mass spectrometry data indicate that bpy accelerates the reaction of platinum with DNA nitrogen, but the resulting adducts are more labile than those formed by the prototype.