[Effect of the molecular structure of natural anthracycline antibiotics on their relative hydrophobicity]. / Vliianie molekuliarnoi struktury prirodnykh antratsiklinovykh antibiotikov na ikh otnositel'nuiu gidrofobnost'.

Relative hydrophobicities of anthracycline antibiotics, adriamycin, rubomycin and carminomycin, have been measured by the two-phase distribution method. Two different biphasic systems were used for this purpose. Possible reasons of discrepancies between results obtained and other authors, data are discussed. It was established that the relative hydrophobicities of the compounds investigated contradict the theory of increment additivity. The results are compared with quantum-chemical calculations.

[Effect of the molecular structure of anthracycline compounds on their intercalation into DNA]. / Vliianie molekuliarnoi struktury soedinenii antratsiklinovogo riada na ikh interkaliatsiiu v DNK.

Kinetics of interaction of rubomycin, carminomycin, and their C9-analogues with deoxyribonucleic acid have been studied by the stop - flow method. Possible reasons of nonexponentiality of the kinetic curves are discussed. The rate constants of direct and reverse intercalation of the drugs between DNA base pairs were determined and relatively small differences found for various drugs. These data and of equilibrium binding studies of interaction of the antibiotics and their analogs with DNA led to conclusion that C9-modification of anthracyclines has little effect on the binding process. That was confirmed by quantum-mechanic calculations of potential energy of interaction between various anthracycline aglicones and DNA base-pairs.

[Mechanism of daunorubicin interaction with DNA]. / Mekhanizm vzaimodeistviia daunorubitsina s DNK.

The kinetics of binding of rubomycin and its aglycon (daunomycinon) with DNA was studied with the stopped flow method. It was shown that the reaction of formation of the complex of daunorubicin with DNA involved two stages. At the first stage the antibiotic aglycon intercalated between the pairs of DNA bases and at the second stage the resulting complex was additionally stabilized due to interaction of the positively charged amino sugar residue of the antibiotic with the negatively charged DNA phosphates. The reaction of formation of the complex of daunomycinon with DNA involved one stage. Estimation of the constants characterizing the above reactions is presented.

[Stereochemistry and kinetics of interaction with DNA of the antineoplastic antibiotic olivomycin]. / Stereokhimiia i kinetika vzaimodeistviia s DNK protivoopukholevogo antibiotika olivomitsina.

The kinetics of interaction of antitumor glycoside antibiotic olivomycin with DNA has been investigated. The existence of two relaxation times in the experimental kinetics curves indicates that two types of antibiotic--DNA complex are formed. We have measured the rate constants of association and dissociation processes and determined their temperature dependences. It is suggested, that one of the complex form results from nonspecific interaction between glycoside residues of the antibiotic molecule and sugar-phosphate backbone of DNA whereas the other type of complex exhibits a pronounced specificity for GC-rich regions on DNA. The binding specificity probably results from formation of a H-bond between the antibiotic chromophore ring and guanine 2-amino group. A stereochemical model for olivomycin-DNA complex is proposed. According to this model the antibiotic chromophore and glycoside residues are located in the narrow groove of DNA.

[Interaction of rubomycin and its aglycone with DNA studied by fluorescent methods]. / Issledovanie vzaimodeistviia rubomitsina i ego aglikona s DNK fliurestsentnymi metodami.

The fluorescent characteristics of rubomycin as dependent on the environmental conditions (different solvents, acidity of the medium, ionic strength) were studied. A model explaining suppression of the rubomycin fluorescence on the antibiotic interaction with DNA is described. The model confirmed intercalation and preferable binding with purines as compared to pyrimidines. The constants of rubomycin and aglycone interaction with DNA were determined. The use of the antibiotic concentrations less than 10(-6) M allowed the determination of a higher constant characterizing "strong binding". The nonlinearity of the curve of DNA titration with the antibiotic plotted on the Scatchard coordinates indicates the heterogeneity of the binding sites. The constant of the aglycone binding to DNA was approximately 2 orders lower at the same number of the binding sites in one molecule. The decrease in the constant of rubomycin interaction with DNA of an increased ionic strength and the low constant of the aglycone interaction with DNA as compared to that of the antibiotic itself confirmed the suggestion that there formed a bond between the amino sugar and the phosphate groups.

[Luminescence absorption properties of the olivomycin molecule and its complex with DNA]. / Liuminestsentno-absorbtsionnye svoistva molekuly olivomitsina i ee kompleksa s DNK.

Olivomycin (I) is a fluorescent probe which is highly specific with respect to DNA. Its luminescence-absorption properties were studied at various pH values, in different solvents and in the presence of Mg2+ and DNA in the solutions. The presence of 2 tautomeric forms of I was suggested on the basis of the study (forms A and B having different characteristics with respect to the absorption spectra and fluorescence). Transition between forms A and B occurred in both the basic and the excited states. The quantitative ratio of the forms depended on the character of the environment. The presence of the 2 forms of I should be considered in analysis of the drug pharmacokinetics and pharmacodynamics.