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

Abstract

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 (23Me₂dpq) 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)]Cl₂ and [Pt(dpq)(RR-dach)]Cl₂, with IC₅₀ values of 0.19 and 0.80 μM, respectively. The X-ray crystal structure of the complex [Pt(dpq)(SS-dach)](ClO₄)₂·1.75H₂O is also reported.