Studies on the interaction between antitrypanosome cis-DDP analogs with DNA.

The nature of the conformational changes produced in DNA by cis-DDP analogs has been studied by physiochemical techniques. The UV spectra showed that the DNA undergoes bathochromic shifts accompanied by hyperchromic effects in reaction with specific analogs (cis-Pt(DDH) (mucobromic)2, cis-Pt(tranilcypromine)2Cl2 and cis-Pt(DDH) Cl2), while a different series of analogs (cis-Pt(DDH) (metafluorobenzoic)2 and cis-Pt(pentamidine)Cl2) induce a significative decrease in the absorbance at 258 nm. Moreover one of these analogs (cis-Pt(pentamidine)Cl2) causes strong stabilization of the double helix to heat denaturation. The CD spectra indicate moreover that cis-Pt(pentamidine)Cl2 modifies the secondary structure of the DNA in a significant way with an increase of the positive band and a decrease of the ellipticity of the negative band. The antitrypanosome activity of cis-Pt(pentamidine)Cl2 is probably due to inhibition of the intracellular parasites division in parasitized cells.