Structure-antifungal activity relationships of polyene antibiotics of the amphotericin B group.

A comprehensive comparative analysis of the structure-antifungal activity relationships for the series of biosynthetically engineered nystatin analogues and their novel semisynthetic derivatives, as well as amphotericin B (AMB) and its semisynthetic derivatives, was performed. The data obtained revealed the significant influence of the structure of the C-7 to C-10 polyol region on the antifungal activity of these polyene antibiotics. Comparison of positions of hydroxyl groups in the antibiotics and in vitro antifungal activity data showed that the most active are the compounds in which hydroxyl groups are in positions C-8 and C-9 or positions C-7 and C-10.

Synthesis and study of the antifungal activity of new mono- and disubstituted derivatives of a genetically engineered polyene antibiotic 28,29-didehydronystatin A1 (S44HP).

Mono- and disubstituted novel derivatives of the heptaene nystatin analog 28,29-didehydronystatin A(1) (S44HP, 1) were obtained by chemical modification of the exocyclic C-16 carboxyl and/or an amino group of mycosamine moiety. The strategy of preparation of mono- and double-modified polyene macrolides was based on the use of intermediate hydrophobic N-Fmoc (9-fluorenylmethoxycarbonyl) derivatives that facilitated the procedures of isolation and purification of new compounds. The antifungal activity of the new derivatives was first tested in vitro against yeasts and filamentous fungi, allowing the selection of the most active compounds that were subsequently tested for acute toxicity in mice.

[Isolation and study of antibiotic INA-1132 (chlorothricin), produced by actinomycete strain].

Taxonomic properties of strain INA-1132 producing antibiotic INA-1132 are described. The antibiotic showed activity against grampositive bacteria and fungi. The strain was classified as belonging to the genus Streptomyces and by its taxomic characteristics is most close to S.

Chemical modification and biological evaluation of new semisynthetic derivatives of 28,29-Didehydronystatin A1 (S44HP), a genetically engineered antifungal polyene macrolide antibiotic.

Twenty-three new derivatives of the heptaene nystatin analogue 28,29-didehydronystatin A(1) (1) (S44HP) were obtained by chemical modification of C16 carboxyl and amino groups of mycosamine. These derivatives comprised 15 carboxamides, 4 N-alkyl derivatives, 3 N-derivatives containing additional N-linked monosaccharide or disaccharide moiety (products of Amadori rearrangement), and 1 N-aminoacyl derivative. The derivatives have been tested in vitro against yeasts Candida albicans, Cryptococcus humicolus, and filamentous fungi (molds) Aspergillus niger and Fusarum oxysporum, as well as for hemolytic activity against human erythrocytes.

[Echinomycin production by Actinomadura sp. INA 654].

An actinomycete strain designated as Actinomadura sp. INA 654 was isolated from a chernozem soil sample in the Voronezh Region by the soil sample treatment with millimetric waves (EHF band). The strain produced an antibiotic complex of 2 components, named A-654-I and A-654-II.

Rare actinomycete bacteria from the shallow water sediments of the Trondheim fjord, Norway: isolation, diversity and biological activity.

Actinomycete bacteria produce a wide variety of secondary metabolites with diverse biological activities, some of which have been developed for human medicine. Rare actinomycetes are promising sources in search for new drugs, and their potential for producing biologically active molecules is poorly studied. In this work, we have investigated the diversity of actinomycetes in the shallow water sediments of the Trondheim fjord (Norway).

[The application of succession analysis in combination with extremely high-frequency irradiation to the selective isolation of actinomycetes from soil].

A new method employing succession analysis and extremely high-frequency (EHF) irradiation is proposed for the selective isolation of actinomycetes from soil. Total actinomycetes were efficiently isolated from soil suspensions irradiated in the wavelength band 4.6-5.

[Actinoplanes brasiliensis INA 3802--a producer of peptide antibiotics].

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.

Teichuronic acid of the cell wall of Actinoplanes brasiliensis.

The cell wall of Actinoplanes brasiliensis INA 3802 contains a teichuronic acid of unusual structure, as determined in a nondestructive way by 1H- and 13C-NMR spectroscopy. The polysaccharide comprises six tetrasaccharide units of the following composition: -->6)-alpha-D-Glcp-(1-->4)-beta-D-2,3-diacetamido- 2,3-dideoxyGlcpA-(1-->4)-alpha-D-2,3-diacetamido-2,3-dide oxyGlcp-(1-->4)-beta- D-2,3-diacetamido-2,3-dideoxyManpA. A polymer of such structure has not heretofore been reported for procaryotic cell walls.

167-A, a new antibiotic produced by a mutant of an inactive wild strain of Amycolata autotrophica.

Two related antibiotics, 167-A and 167-B, were isolated from the fermentation broth of a mutant of an inactive wild strain of Amycolata autotrophica. Antibiotic 167-B was found to be cervinomycin A2; antibiotic 167-A is a new representative of the same group and has the structure of 18-O-demethyl cervinomycin A2.

[An anionic polysaccharide from the cell wall of Actinoplanes brasiliensis INA 3802].

The cell wall of Actinoplanes brasiliensis INA 3802 contains a polysaccharide which has an unusual structure. The peculiar structure of the polymer has been established by a nondestructive procedure which included 1H- and 13C-NMR spectroscopy. The polysaccharide consists of six tetrasaccharide links having the following composition -->6(alpha-D-Glc rho-(1-->4)-beta-D-Clc rho 2,3NAcA-(1-->4)-alpha-D-Clc rho 2,3NAc-(1-->4)-beta- D-Man rho 2,3NAcA-(1-->.

[Production of griseoviridin and etamycin by the new culture, Streptomyces albolongus].

An actinomycete strain designated as 4297 was isolated from a soil sample collected near Moscow. The strain produced a complex of two antibiotics. One of them had a broad antibacterial spectrum and, in terms of its physicochemical properties and X-ray structural evidence, was identified with griseoviridin.

[Comparative evaluation of various bacterial growth inhibitors as selective agents for isolation of soil Actinomyces].

Tobramycin and dioxidine sensitivity of 57 strains belonging to 14 actinomycetes genera was studied. The cultures of Streptomyces were much more sensitive to tobramycin than the cultures of rare genera. The majority of the Streptomyces cultures showed a high resistance to dioxidine (MIC greater than or equal to 50 micrograms/ml).

[Actinomadura species as antibiotic producers].

Screening of antibiotic-producing cultures among Actinomadura showed that definite species mainly produced antibiotics of the same groups. Thus, carminomycins were produced by all the 4 studied strains of A. carminata, maduramycins were produced by 3 strains of A.

[Isolation of antibiotic-producing Actinomycetes from soil samples exposed to UV light].

The use of nonroutine means in isolation of microorganisms from natural substrates extended the possibilities of detecting new cultures which often appear to be producers of previously unknown antibiotics. A new procedure for isolating actinomyces of definite groups was developed. It implies preliminary exposure of soil suspensions to UV light.

[Antibiotics formed by Actinomadura fulvescens].

Novel antibiotics with in vitro activity against gram-positive bacteria were isolated from Actinomadura fulvescens INA 3321 and INA 3852. Conditions for biosynthesis and isolation of antibiotics 3321 and 3852, as well as their physicochemical and biological properties were studied. Chromatographic analysis of the antibiotics revealed that each of them contained two biologically active components.

[Formation of a streptothricin-group antibiotic by a Streptomyces glaucus 1136 culture].

In screening of new antibiotics a streptomycete (strain 1136) was isolated from a soil sample of Armenia. It showed no antagonistic properties in streek cultures on agarized media. When grown under submerged conditions strain 1136 produced an antibiotic active against grampositive and gramnegative bacteria.

[New species of Actinomadura recticatena sp. nov. and its antibiotic properties].

Actinomadura cultures were isolated from soil samples collected in Turkmenistan, the Moscow, Kursk and Volgograd regions. The cultures were described as representatives of a new species (Actinomadura recticatena, Preobrazhenskaya et Galatenko, sp. nov).

[Distribution of actinomycetes of the genus Actinomadura in the light chestnut soils of Volgograd Province and their antagonistic properties].

Prevalence of the actinomycetes of the Actinomadura genus in the virgin and cultivated light chestnut soils of the Volgograd Region was studied. It was shown that Actinomadura were one of the constituents of the actinomycetous flora of these soils. No significant changes in the number of the Actinomadura and the total number of the actinomycetes were observed in the cultivated and virgin soils.

[New species, Actinomadura fulvescens sp. nov. and Actinomadura turkmeniaca sp. nov. and their antagonistic properties].

Two new species of Actinomadura isolated from soil samples of the Turkmen SSR, i.e. Actinomadura fulvescens sp.

[Number, species composition and antagonistic properties of Actinomadura from soddy-podzolic soils and from soils in the tundra zone].

Occurrence of Actinomadura in the turf-podzol soils of the Moscow region and in the tundra soils of Taimir was studied. It was found that there were practically no Actinomadura in the tundra soils, while their occurrence in the turf-podzol soils was rather high and amounted to 5 per cent of the actinomycetous flora. The occurrence of Actinomadura in cultured soils was higher and their species composition was more diverse as compared to those in virgin lands.

[New species of Actinomadura isolated from soils in Turkmenia and their antagonistic properties].

New species, i.e. Actinomadura polychroma and Actinomadura umbrina are described.