Synthesis and analysis of the anticancer activity of platinum(II) complexes incorporating dipyridoquinoxaline variants

Eight platinum(II) complexes with anticancer potential have been synthesised and characterised. These complexes are of the type [Pt(I-L)(A(L))](2+), where I-L is either dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) or 2,3-dimethyl-dpq (23Me(2)dpq) and A(L) is one of the R,R or S,S isomers of either 1,2-diaminocyclohexane (SS-dach or RR-dach) or 1,2-diaminocyclopentane (SS-dacp or RR-dacp). The CT-DNA binding of these complexes and a series of other complexes were assessed using fluorescent intercalator displacement assays, resulting in unexpected trends in DNA binding affinity. The cytotoxicity of the eight synthesised compounds was determined in the L1210 cell line; the most cytotoxic of these were [Pt(dpq)(SS-dach)]Cl-2 and [Pt(dpq)(RR-dach)]Cl-2, with IC50 values of 0.19 and 0.80 mu M, respectively. The X-ray crystal structure of the complex [Pt(dpq)(SS-dach)](ClO4)(2)center dot 1.75H(2)O is also reported.