[A search for microscopic fungi with directed hydroxylase activity for the synthesis of steroid drugs].

The hydroxylase activities of new strains such as Curvularia lunata, C. geniculata, C. eragrostidis, C. prasadii, Ulocladium botrytis, Alternaria tenuis, and Fusarium oxysporum toward three steroid substrates, namely, androstenedione (AD), cortexolone (S), and dehydroepiandrosterone acetate (DAA), were characterized. The 9α-hydroxylase activity of C. lunata 1011 cells against S to form 9α-hydroxy-S was shown for the first time. It was found that C. geniculata 837 and F. oxysporum 11dn1 strains can hydroxylate substrates to form pharmacologically promising 7α-hydroxysteroids. C. geniculata 837 cells selectively hydroxylate AD, resulting in 7α-hydroxytestosterone, whereas F. oxysporum 11dn1 leads to the transformation of DAA to 7α-hydroxydehydroepiandrosterone.

[Novel Immobilized Biocatalyst for Microbiological Synthesis of Pharmaceutical Steroids].

The steroid-transforming activity of free and immobilized cells of Pimelobacter simplex VKPM As-1632 entrapped in an operationally stable macroporous polyvinyl alcohol cryogel was studied. It was shown that the macroporous matrix of the carrier did not create any diffusional limitations for steroid access to the cells or the removal of the transformation products from them. The optimal conditions for the hydrocortisone 1,2-dehydration into prednisolone by free and immobilized cells were elucidated. The immobilized biocatalyst was obtained in a granulated form and used in 32 successive cycles of steroid transformation. The average cycle duration was 45 min, and the prednisolone yield of during the first 20 cycles was 98%. It was established that the immobilized cells of the actinobacteria P. simplex retained high steroid-transforming activity over all of the transformation cycles. The physicochemical and diffusion characteristics of the polyvinyl alcohol gels and its granules were determined, and their high stability during repeated cycles of steroid transformation was shown. The results indicated that P. simplex immobilized cells represent an effective catalyst suitable for multiple use. Biomass consumption decreased upon its use, and product isolation, as well as culture storage, was much easier.

[Transformation of delta4-3-ketosteroids by free and immobilized cells of Rhodococcus erythropolis actinobacterium].

9alpha-Hydroxy derivatives were prepared from 11 steroids ofandrostane and pregnane series using Rhodococcus erythropolis VKPM Ac-1740 culture with 0.5-20 g/l substrate concentration in the reaction mixture. 9alpha-Monohydroxylation proceeded regardless of the substituent structure at C17. However, the structure of the steroid molecule influenced the time of complete conversion of the substrate and the yield of the transformation product. 9alpha-Hydroxy-androstenedione was obtained in 35 h in a yield of 85% when the maximum concentration of androstenedione (AD) was 10 g/l. 9alpha-Hydroxy-AD was also formed by the actinobacterium cells entrapped in poly(vinyl alcohol) cryogel beads. Nine successive transformation cycles were carried out using immobilized cells at 4.0 g/l concentration of AD in the medium. The yield of 9alpha-hydroxy-AD formed during six cycles (from two to eight with the duration of each cycle for 22-24 h) was 98%.

[Acilact and improvement of the health status of sickly children].

A complex study of the effects of Acilact on the immune and interferon status, phagocyte defense, and cytokine balance in sickly children showed that Acilact had a positive effect on the immune system in these patients. The preparation is able to normalize abnormal immune parameters, and does not influence healthy immune system. In some ways Acilact has advantages over IRS 19 vaccine. Simultaneous administration of these two preparations is appropriate in some cases.