The interaction of calf thymus DNA (ST DNA) with the cluster rhenium compounds with phosphate, adamantyl and ferrulate ligands was studied by the electron spectroscopy for the first time. During the spectrophotometric titration of CT-DNA with the compounds of direnium Retetraphosph, Recis-Adam, Retrans-Adam, ReFerul, the hyperchromic effect in the region of 260 nm of DNA was observed, it is much higher than that shown for binuclear alkyl carboxylates of rhenium (III).
The DNA-ligand complexes formation in the long-wavelength region of the spectrum, which is due to the interaction of π-electron clouds of nucleic bases and biologically active ligands, was shown for the first time. The dependence of the interaction mechanism of rhenium compounds and DNA in the presence of hydrogen peroxide and cisplatin in solutions was shown. Spectrophotometric titration of rhenium compounds in the presence of cisplatin was performed for the first time and binding constants were obtained This constants exceed the values of the basic constants, especially for ReFerul (almost 12 times). For the first time, the method of competitive complexation with propidium iodide showed that cluster rhenium (III) compounds of different structural types are able to interact with oligonucleotides with the intensity which exceeding the intensity of cisplatin
binding, depending on the structure of the ligands, the intensity of the interaction reaches 73.2%. The cytotoxic activity of a new cluster compound of rhenium with
beta-alanine ligands [Re2Cl6(C3H7NO2)2]·1.5H2O (Recis-βAla) in solutions and nanoliposomes separately and together with cisplatin on leukemic T-cells of the
Jurkat line was studied for the first time. It is shown, that Recis-βAla solution has a cytotoxicity close to the IC50 value to cisplatin (IC50 = 2,06·10-6 M). The administration of the rhenium-platinum system with Recis-βAla showed even greater cytotoxicity against cells, especially high when both components of the system were in the form of mixed liposomes (IC50 = 4,93·10 -10 M). Loaded with both cytostatics liposomes (nanobins) were used in experiments with cancer cell culture first time and showed high efficacy. It is shown that in the presence of Recis-βAla by different methods of administration, even at significant (necrotic) concentrations of cisplatin, the apoptotic pathway of leukemic T-cells of the Jurkat line death are predominates. This is very important for therapeutic measures and side effects, as necrosis activates inflammation and the immune
response, which is not inherent in apoptosis. The anticancer, DNA-binding and antioxidant activities of the rhenium cluster compound with β-alanine ligands have been studied.. The high solubility and stability of the substance in aqueous solutions, in contrast to alkylcarboxylates, revealed the effect of its aqueous solution and the rhenium-platinum system based on it on the growth of Guerin's carcinoma without the use of liposomes. The introduction of both the solution and the liposomal form of the compound direnium Recis-βAla led to a decrease in tumor mass almost equally, which makes it possible to use water-resistant compounds of direnium in experimental work and practice. It was found that the newly synthesized cluster compound of rhenium Recis-βAla, regardless of the method of administration has antioxidant and antianemic properties in vivo, stabilizing a red
blood cell counts, as was the case with other rhenium (III) cluster compounds. In general, elucidation of the anticancer, DNA-binding, and antioxidant properties of such compounds opens up new, broader prospects for the introduction of amino acid derivatives of rhenium (III) cluster compounds into medical practice.
The antitumor activity of two derinium (III) dicarboxylates with 1-adamantanecarboxylic acid ligands, with cis- and trans-orientation of carboxyl groups around the cluster fragment of cis- and trans-diadamants of dirhenium separately and together with cisplatin in vivo was studied. The antitumor activity was almost identical to the minor benefits for the cis analog in vivo. The attempt to explain the differences in the possible mechanism of antitumor activity of substances taking into account the antiradical and DNA-binding properties of the studied compounds was made.
