INFLUENCE OF CATIONIC PORPHYRINS ON CISPLATIN-MODIFIED DNA

Abstract

The antitumor activity of cisplatin is achieved through covalent binding to DNA. To eliminate systemic toxicity and side effects, studies of cisplatin–DNA complexes are often conducted in combination with other drugs that selectively accumulate in tumor tissues without forming covalent bonds with DNA and are easily excreted from the body. In the present study, the interactions of the cationic porphyrins H2TOEtPyP4 and ZnTOEtPyP4 with platinated DNA were investigated in comparison with native DNA. Thermal melting curves show that the porphyrin ZnTOEtPyP4 stabilizes the platinized DNA double helix much better than H2TOEtPyP4. UV-CD spectra show that ZnTOEtPyP4 induces structural changes in the DNA double helix similar to the B-Z transition. This twisting of the DNA molecule occurs due to an increase in the binding ability of porphyrins to DNA. The binding constants of the studied porphyrins with platinated DNA are approximately twice as large as with native DNA. However, the small value of the exclusion parameter (n<2) shows that the ZnTOEtPyP4 porphyrin molecules at high concentrations are located in greater quantities on the surface of the platinated DNA molecule and stabilize it.