[Glycol and Phosphate Depot Forms of 4- and/or 5-Modified Nucleosides Exhibiting Antibacterial Activity].

Resistance developed to the majority of drugs used to treat infectious diseases warrants the design of new compounds effective against drug-resistant strains of pathogens. Recently, several groups of modified nucleosides have been synthesized and showed significant antibacterial activity in vitro, but their further studies were difficult to undertake because of their low solubility in aqueous solutions. Nevertheless, new compounds, well soluble in water-organic solutions, were synthesized and found to be more effective in inhibiting the growth of Gram-positive bacteria and mycobacteria. The water-soluble forms of modified nucleosides under study were assumed to be their depot forms. To check the assumption, the compounds were tested for hydrolysis in various media and their molecular docking was performed into the active center of the putative target, Mycobacterium tuberculosis flavin-dependent thymidylate synthase ThyX. Computer modelling showed that the water-soluble analogs do not act as ThyX inhibitors, supporting the assumption of their depot nature. The compounds were resistant to chemical hydrolysis but were hydrolyzed when incubated with porcine liver carboxylesterase, human serum, or Staphylococcus aureus 209P. The results demonstrate that the compounds are most likely depot forms of modified nucleosides.

Development of Liposomal Forms of Modified Pyrimidine Nucleosides and Investigation of Their Antibacterial Properties.

Different phosphocholine-cardiolipin-2'-deoxyuridine inclusion complexes were developed, that allowed to compose a water-soluble form of nucleoside analogues with previously defined antituberculosis activity. It was found that the resulting liposomes effectively penetrated to the cells. The increase of cytotoxicity was undoubtedly indicative of accumulation of the nucleoside in the cell culture. The result proved the ability of the liposomes for delivery of the low-soluble compounds to the cells for further investigation of their efficacy. It was shown that treatment of the bacterial cells with the llposomes of the modified nucleosides did not affect the bacterial growth.

[Search for A factor-dependent variants in actinomycete population]. / Poisk A-factorzavisimykh variantov v populiatsiiakh aktinomitsetov.

A study of 28 nocardia-like, asporogenous, and oligosporous spontaneous morphological variants belonging to 23 species of streptomycetes revealed five strains producing regulators of the A-factor group. Streptomyces griseus 1439, which forms aerial mycelium and spores only in the presence of exogenous A-factor was used as the test strain. Among the 28 spontaneous variants, three new A-factor-dependent strains were revealed, which represented the species Streptomyces griseus, S. citreofluorescens, and S. viridovulgaris subsp. albomarinus. These weakly differentiated variants id not produce A-factor and behaved as its recipients, responding by changes in their morphological characteristics at a concentration of this regulator in the medium of 0.01 microgram/ml and higher. The original collection strains in whose populations the variants were selected produced substances of the A-factor group. The A-factor-dependent variants differed in the level of the regulator required for maximal expression of the morphological characteristics were shown: it was necessary to introduce the A-factor at a concentration of 1 microgram/ml for S. citreofluorescens and S. viridovulgaris subsp. albomarinus and at 10 micrograms/ml for S. griseus.

[Actinoplanes brasiliensis INA 3802--a producer of peptide antibiotics]. / Actinoplanes brasiliensis INA 3802--produtsent peptidnykh antibiotikov.

In the screening programme for new antibiotics an actinomycete culture designated as 3802 was isolated from a soil sample. The culture produced a complex of peptide antibiotics belonging to the group of lantibiotics. The antibiotic complex included gardimycin (actagardin) and new antibiotics of the same group. By the taxonomic properties strain 3802 was classified as Actinoplanes brasiliensis not previously known to produce gardimycin. Conditions of the antibiotic complex biosynthesis by strain 3802, the isolation methods and biological properties were studied.