Results of the clinical study of the antineoplastic antibiotic bleomycetin

Bleomycetin was applied to the treatment of 68 patients with common forms of malignant tumors. The objective therapeutic effect was observed in 21 patients (31 per cent). The frequency of the favourable therapeutic effects was the most significant in the group of patients with generalized forms of lymphogranulomatosis: objective remissions for 1 to 4 months and stabilization of the tumor process were attained in 12 (41 per cent) and 8 out of 29 patients, respectively, in 9 patients (31 per cent) treated with bleomycetin progression of the underlying disease was recorded. A less pronounced therapeutic effect (33 per cent of the remissions) was recorded in the patients with nonlymphogranulomatous lymphomas. The use of bleomycetin in 48 out of 68 patients was complicated by certain adverse reactions. Intravenous infusions of bleomycetin in a dose of 10-15 mg twice a week (the total dose up to 125 mg) may be recommended as the initial therapeutic regimen in the oncological practice. The trials have showed that bleomycetin made in the USSR has a sufficiently pronounced activity against lymphogranulomatosis and nonlymphogranulomatous lymphomas. In this respect it is not inferior to the bleomycin analog made in Japan.     

Structure of the antineoplastic antibiotic variamycin]

The results of the structural study of antitumor antibiotic variamycin and its peracetyl derivative by 1H-and 13C-NMR spectroscopy are reported. Structures of carbohydrate chains of the antibiotics molecule are revised. Variamycin is shown to be 2-[beta-cymmarosyl(1-3)-beta-oliosyl (1-3)-beta-olivosyl]-6-[beta-olivosyl (1-3)-beta-olivosyl] chromomycinone.     

Cytogenetic effect of the antineoplastic anthracycline antibiotic 4'-epidoxorubicin

Cytogenetic action of 4'-epidoxorubicin (farmorubicin), an antitumor antibiotic was studied with using rat bone marrow cells. It was shown that after intraperitoneal administration the antibiotic increased the number of the aberrant metaphases when the dose was not lower than that equivalent to 1/30 of the LD50. The number of the aberrant metaphases increased with increasing of the antibiotic dose. The maximum number of the cells with impaired chromosomal apparatus was observed 6 hours after the antibiotic administration. In 72 hours it decreased to the level of spontaneous mutations in myelocariocytes. Cytogenetic activity of 4'-epidoxorubicin was comparable to that of doxorubicin (adriablastin) widely used in medical practice.     

Physicochmemical characteristics of the new antineoplastic antibiotic, nocamycin]

Nocamycin is produced by Nocardiopsis syringae. It is recovered from the culture fluid by extraction with chloroform. The molecular weight of the crystalline antibiotic is 503, its melting point is 147--149 degrees, [alpha]20 degrees D = --50 degrees (c. 0.21, chloroform), lambdamax235 and 348 nm(E1%sm= = 150 and 420), the summation formula is C26 H33NO9, the biological activity is 100000 Units/mg with respect to Bacillus mycoides. Nocamycin forms salts with alkalies soluble in water. On hydrolysis with an alkali it forms carbonic acid having no ester bond (IP spectrum) and methoxylic group present in the antibiotic molecule. Nocamycin is a new natural substance.     

Stereochemistry and kinetics of interaction with DNA of the antineoplastic antibiotic olivomycin

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.     

Effect of the antineoplastic antibiotic bruneomycin on lymphocyte population ratio in mice

Data on the quantitative ratio of the populations of T- and B-cells in the lymphoid organs of mice at various periods after oral administration of bruneomycin are presented. It was shown that in contrast to the total number of T- and B-cells in the spleen and mesenteric lymph nodes amounting to the minimal values at the early periods (days 1-3) after the antibiotic injection, their relative content remained rather high. Complete recovery of the number of T- and B-lymphocytes in the above organs was observed only by the end of a month period. Study on the kinetics of the immune response to sheep red blood cells showed that reactivity of the antibody producers in the experiments with bruneomycin increased 1.5-2 fold as compared to the control.