Anti-tumour platinum acylthiourea complexes and their interactions with DNA

The interactions of a series of anti-tumour platinum acylthiourea complexes of formula [Pt(L)Cl(DMSO)] (HL= R′C(O)NHC(S)NR₂; R′ = aryl, NR₂ = amine) with natural and synthetic DNAs and with nucleotides were investigated. Circular dichroism experiments confirmed binding and linear dichroism showed that the binding is specific (rather than random), leading to orientation of the complexes on the DNA and resulting in bending of the DNA. Mass spectrometry confirmed coordination of the platinum to the nitrogen-containing base of the nucleic acids with the displacement of chloride. No evidence was obtained for bis-substitution involving concomitant loss of the chloride and DMSO. The mode of binding of the platinum to DNA is affected by the nature of the substituents on the acylthiourea, but this behaviour does not correlate with the biological activity observed.