Исследовали действие олигомицинов SCII и В на пролиферацию и апоптоз клеток лимфолейкоза Р388 и штамма, устойчивого к винкристину. Показано, что оба олигомицина в низких концентрациях: олигомицин В – до 0.3, олигомицин SCII – до 1 нг/мл подавляют пролиферацию клеток. В больших концентрациях олигомицины вызывают гибель клеток по типу апоптоза, причем чувствительность к олигомицинам клеток дикого типа и штамма, устойчивого к винкристину, одинакова. Олигомицин В в 3 раза более эффективно снижал выживаемости клеток, чем олигомицин SCII: IC50 составляет 3 и 10 нг/мл соответственно. Одинаковая чувствительность к олигомицинам клеток дикого типа и штамма, устойчивого к винкристину, объясняется тем, что олигомицины ингибируют множественную лекарственную устойчивость опухолевых клеток, что показано по увеличению скорости образования кальцеина из ацетооксиметилового эфира кальцеина в клетках устойчивого штамма.

Сравнили влияние олигомицинов SсII, F, В и циклоспорина А на множественную лекарственную устойчивость (МЛУ) клеток лимфолейкоза Р388BР и клеток рака гортани HEр-2. Установлено, что олигомицин SсII снижает откачку родамина 123 и кальцеина АМ из клеток НЕр-2 эффективнее, чем циклоспорин А, а в клетках Р388ВР циклоспорин А был эффективнее олигомицинов. Различия в эффективности циклоспорина А и олигомицинов в клетках разного типа, по-видимому, обусловлена экспрессией в них разных транспортных белков: Pgp в Р388ВР и других белков (например, одного из семи белков семейства MRP) в НEр-2.

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.

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.

Natural complex compounds with hipolipidemic activity, having considerable inhibitory effect on expression of bacteria virulence factors were isolated. Inhibitory properties of the compounds with respect to pyocyanine and protease formation, as well as their influence on the quorum sensing mechanism in Chromobacterium violacium were shown.

The review deals with cyclodepsipeptides produced by hyphomycetes. The cyclodepsipeptide compounds are prospective new agents for the treatment of diseases of the infectious and pathophysiologic nature.

: The frequence of mutations in the rifampicin resistant (RIF(r)) clones of microorganisms after adaption to ofloxacin and metronidazole was investigated to estimate the biological cost of H. pylori rifampicin (RIF) resistance. Mutations in rpoB gene responsible for RIF resistance of H. pylori were shown to have biological cost and be compensated by additional mutations in the microorganism genome. Comparison of the mutation frequency in the presence of metroniazole demonstrated that the acquired resistance to RIF resulted in changing of the adaptative capacity of the RIF(r) clones of H. pylori to metronidazole. Thus, a significant increase of the mutation frequency (> 700 times) in one of the RIF(r) clones and a broad spectrum of the mutations responsible for resistance to metronidazole vs. the H. pylori initial strain 26695 were observed. The findings could be evident of the fact that the adaptation to RIF changed the properties of the cell on one hand in such a way that its mutation capacity increased and that the target selection on the other hand revealed hypermutable cells, likely usual for the bacterial population.

Natural compounds showing considerable inhibitory effect on formation of biofilms by P. aeruginosa were selected. Synergism of the compounds with gentamicin with respect to both the inhibition of the biofilm formation and the gentamicin antibacterial effect was stated.

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.

Complex compounds produced by fungal cultures of Lecanicilium and Beauveria with both high hypolipidemic and antioxydant activities were screened. Two fractions of the hypolipipidemic compounds with antioxidant activity of 95 and 75% in a dose of 25 mcg/ml were isolated.