[Screening of Organisms Producing Inhibitors of 15-Lipoxygenase Among Micromycetes.]

The effects of extracts from the mycelium of Lecanicilium lecaniiNo.169, Beauveria fellina No.7 and Beauveria bassianaNo.15 on the activity of 15-lpoxygenase (15-LO) recovered from rat reticulocytes was investigated. The activity of 15-LO was determined by oxidation of linolic acid. The extract from the mycelium of the fungal complex was shown to inhibit 15-LO (IC50 of 12 mcg/ml). The inhibitory effect of the combined extract on 15-LO was due to the substances recovered from Lecanicilium lecanii No.169. The extract fractions responsible for the activity were determined and the compounds containing the fractions were identified. They proved to be 10 - 4-hydroxybenzoic acid and 4-hydroxybenzyl alcohol and genistein, a flavonoid from fraction 11. The possible role of the inhibitory effect of the compounds on 15-LO in the antiatherosclerotic activity of the fungal extract is discussed.

[Determination of oligomycins hydrophobicity parameters].

The parameters of hydrophobicity of five oligomycins, i. e. A, B, C, F and SC-II were determined by HPLC. The location of the ascending hydrophobicity parameter was set: oligomycin B < oligomycin SC-II < oligomycin A < oligomycin F < oligomycin C.

[Physico-chemical properties and structure of oligomycin SC-II, produced by Streptomyces virginiae 17].

Under the screening programme for antibiotics with antifungal and immunosuppressive activities, Streptomyces virginiae 17 producing an oligomycin complex was isolated. Separation of the complex by HPLC showed that it contained two components at a ratio of 8:2. The physico-chemical characteristics of the components were investigated. The structure of oligomycin was assessed by 13C NMR and 1H NMR.

[Streptomyces sp. 17, an organism producing oligomycin SC-iI (culture characteristics and antibiotic biological properties)].

Under the screening programme for organisms producing substances with hypolipidemic and antifungal activity Streptomyces sp. 17 was isolated. The taxonomic properties of the strain were investigated. Active compounds, i.e. oligomycin A and oligomycin SC-II were isolated from a complex biosynthetic product. Oligomycin A showed high antifungal activity whereas oligomycin SC-II had also moderate antibacterial activity.

[Production of destruxins by coprotrophic Beauveria feline no. 7 strain].

Beauveria feline No. 7 strain was isolated from the shrewmouse wool and characterized by production of a complex of destruxins cyclodepsipeptides. The strain was shown to produce significant quatities of destruxin B and pseudodestruxin C. The destruxins were found to be able to inhibit formation of biofilms by Pseudomonas aeruginosa ATCC 27833.

[Complex of cyclosporins produced by Tolypocladium inflatum isolated from soil sample from Buriatiia].

A micromycete culture was isolated from a soil sample of Buryatiya and identified as Tolypocladium inflatum No. 2. The culture was shown to produce a complex of cyclosporins of unusual component structure: the content of cyclosporin A (55-60%) was the same as that in the substances produced by the majority of the described cultures, the content of cyclosporin B was much higher (about 40%) and the content of cyclosporin C was relatively low (about 3%). An appreciable content of cyclosporin (Leu4)Cs (3%) proved to be of interest.

[Lovastatin effect on ergosterol production and growth of Tolypocladium inflatum 106]. / Vliianie lovastatina na rost i obrazovanie érgosterola kul'turoi Tolypocladium inflatum 106.

The effect of lovastatin on Tolypocladium inflatum 106 was studied. The strain was shown to be highly sensitive to lovastatin when its MIC was determined by the agar diffusion method and under submerged conditions that was considered possible to use the strain as a test culture in screening of new natural compounds with hypolipidemic action and to study its specificity. It was demonstrated that the effect of lovastatin on ergosterol synthesis in T. inflatum 106 was of specific dose-dependent polymodal nature.

[Screening of natural compounds with hypolipidemic activity]. / Skrining prirodnykh soedinenii s gipolipidemicheskoi aktivnost'iu.

In the screening programme for natural hypolipidemic compounds 702 strains of soil microorganisms were tested and 25 of them were selected because of their ability to produce compounds inhibiting sterol synthesis in Hep G2 hepatoma cells. The compounds were estimated in the microbiological model with Tolypocladium inflatum 106 as the test microbe. The 2nd stage of the screening resulted in isolation of 13 strains producing compounds with high hypolipidemic activity, analogous to or higher than the activity of lovastatin in the experimental models.

[Streptomyces griseolus # 182--a novel organism producing oligomycin antibiotics. Taxonomy, fermentation, and isolation]. / Novyi produtsent antibiotikov oligomitsinovoi struktury Streptomyces griseolus No 182. Taksonomiia, fermentatsiia i vydelenie.

Target screening of natural immunosuppressors resulted in isolation of a strain of Streptomyces griseolus (No. 182) producing a complex of antifungal antibiotics. The strain proved to be an aerobe with the growth temperature of 26 to 28 degrees C. Morphological features and physiological properties of the strain were studied. Scanning electron microscopy revealed smooth, oval spores 1.10-1.25 mu in size. The findings showed that the strain belonged to Streptomyces griseolus. Unlike the previously described organisms producing the oligomycin complex the new strain formed straight or twisted sporophores and did not produce melanoid pigment or soluble pigment when grown on the Gauze mineral agar medium No. 1. The procedures for biosynthesis and chemical recovery of the antibiotic complex from the mycelium are described. The complex was shown to include 3 components at a ratio of 80:15:5 identified as oligomycins A, B and C respectively. The oligomycin complex was highly active against Aspergillus niger 137, Tolypocladium inflatum, Fusarium ocsisporum, Curvularia lunata 645 and Trichoderma alba F-32 (MIC 0.1-1.0 mcg/ml). The activity against yeast and bacterial cultures was observed only when the doses were higher than 100 mcg/ml.

[Determination of the structure of the main component of an antibiotic complex produced by Streptomyces griseolus 182]. / Opredelenie struktury osnovnogo komponenta antibioticheskogo kompleksa, obrazuemogo Streptomyces griseolus 182.

In the programme for screening antibiotics with antifungal and immunosuppressing activity a culture of Streptomyces griseolus 182 was isolated. The culture produced a complex of oligomycin structure antibiotics. Individual components of the complex were isolated by HPLC. The complex was shown to contain three components at a ratio of 80:15:5. The findings were compared with the physico-chemical characteristics of the described antibiotics. On the basis of the analysis it was concluded that fraction 2 of the antibiotic complex 182 could be oligomycin A. A detailed comparative investigation of oligomycin A and component 2 with HPLC, FMR, IR spectroscopy and mass spectrometry revealed their identity. The other two components were shown to be oligomycins B and C.

[Effect of H-ATPase stimulators on cyclosporin biosynthesis]. / Vliianie stimuliatorov H-ATFazy na biosintez tsiklosporina.

An analogy was observed between the mechanisms of action of phytohormones on plant cells and cells of the fungus producing cyclosporine. Fusicoccin and cytokinin were shown to have a high stimulating action on the biosynthesis of cyclosporine. The stimulating concentrations of the phytohormones and the time of their maximum effect were determined. The electron microscopic studies demonstrated that an increase in the level of the cyclosporine synthesis correlated with a significant increase in the number of the cells in the state of the coagulation necrosis.

[The impact of migration on regional demography]. / Bliyanie na migratsiyata barkhu formiraneto na regionalnata demografska situatsiya.

PIP: Patterns in internal migration over the past 10 years in Bulgaria are reviewed, and the regional demographic impact is assessed. The authors observe an uneven distribution of the population among regions and an overgrowth of the larger cities. Government policies to regulate internal migration are outlined. (SUMMARY IN ENG AND RUS)^ieng

[Isolation and identification of an antibiotic from culture 8-86]. / Vydelenie i identifikatsiia antibiotika iz kul'tury 8-86.

An antibiotic complex was isolated from culture 8-86 referred to Bacillus. The complex consisted of components 8-86A and 8-86B active against gram-negative organisms. By its physico-chemical properties such as IR and UV spectra, amino acid composition, specific rotation and fatty acid composition component 8-86B was shown to be close to polymyxin F.

[A system for screening natural immunosuppressors]. / Sistema skrininga immunosupressorov prirodnogo proiskhozhdeniia.

Criteria for directed screening of antibiotics with immunosuppressive action were defined. The first stage included screening of cultures producing antiaspergillous antibiotics. At the second stage, the antibiotics whose antifungal activity decreases in the presence of insulin (at the background of calcium salts) and erythromycin and increases in the presence of verapamil were selected. The screening of antibiotic-producing cultures among 123 strains of mycelial fungi and 181 strains of actinomycetes resulted in isolation of 3 fungal cultures and 2 actinomycetes which produced antibiotics corresponding to cyclosporine A as evidenced by thin-layer and high performance liquid chromatographies.

[Growth rate of antibiotic-producing gram-negative bacteria on liquid nutrient media]. / Izuchenie skorosti rosta gramotritsatel'nykh bakterii--produtsentov antibiotikov na zhidkikh pitatel'nykh sredakh.

Glycerol-yeast medium No. 3 may be used as a seed medium in screening of antibiotic-producing strains among Acetobacter, Gluconobacter, Chromobacterium, Agrobacterium, and other genera. The medium is transparent. It provides visual instrumental control of the growth rate of the seed material and estimation of biomass augmentation. The period of the exponential phase growth of the strains tested on medium No. 3 was 2-8 hours. When no growth on medium No. 3 is observed media Nos. 1 and 2 can be used as alternative seed media.

[Spatial configuration of the carbohydrate portion of carminomycins II and III]. / Prostranstvennaia konfiguratsiia uglevodnoi chasti karminomitsinov II i III.

A neutral fragment of the carbohydrate part of the molecule was isolated in the form of a cyclic acetal (3.5-dinitrobenzoate) from carminomycins II and III belonging to anthracyclines. The acetal preserved all the asymmetric centers. Methanolysis of the cyclic acetal resulted in formation of aldol dimethyl acetal and propylene glycol (3,5-dinitrobenzoate) with isolated asymmetric centers. On the basis of the optic and spectral properties of these compounds it was found that carminomycins II and III differed in the configuration of 2 asymmetric carbon atoms, i.e. acetal atom and the atom in propylene glycol. They had configurations of R (--) in carminomycin II and S (+) in carminomycin III. The third asymmetric center of the acetal in both antibiotics was the same, i.e. S(+).

[Structure of the carbohydrate moiety of carminomycins II and III]. / Struktura uglevodnoi chasti karminomitsinov II i III.

Saccharides II and III were obtained on catalytic hydrogenolysis of carminomycins II and III. The saccharides contained daunosamine and a nitrogen-free fragment of unknown structure. Crotonic aldehyde in the form of 2,4-dinitrophenylhydrazone and 1,2-propylenglycol in the form of 3,5-dinitrobenzoate were isolated on acid hydrolysis of the saccharides. The study on the chemical and spectral properties (PMR-spectra) of the saccharides, their N,O-acetates and hydrolysis products suggested the structure of th carbohydrate moiety of carminomycins II and III as a disaccharide of daunosamine and acyclic semiacetal of 2,4-desoxytetrose.

[Structure of the carbohydrate moiety of actinoidins A and B]. / Stroenie uglevodnoi chasti aktinoidinov A i B

The structure of the carbohydrate moiety of actinoidins A and B was found with partial acid hydrolysis (metanolysis) of the antibiotics and their methyl derivatives and the method of periodate oxidation. Actinoidins A and B had 3 carbohydrate branches presented by the residues of monosugars of D-mannopyranose and 2, 3, 6-tridesoxy-3-amino-4-O-methyl-L-arabinopyranose(L-actinosamine) and disaccharide of 2-O-(2, 3, 6-tridesoxy-3-amino-L-arabinopyranosyl)-D-glucopyranose.