Bibikova M V, Grammatikova N E, Tertov V V, Pinegin B V, Chmel' Ia V, Katlinskiĭ A V
National Research Centre of Antibiotics, Moscow.
Antibiot Khimioter. 2003;48(8):3-6.
In the programme for screening sterol synthesis inhibitors with the use of actinomycetes and fungi 702 strains were tested. The effect of alcohol extracts of the mycelium of fungi and actinomycetes at a dilution of 1/10(3) on sterol synthesis by the Hep G2 hepatome cells was determined by incorporation of 3H acetate into sterols and proteins. Lovastatin (200 pg/ml) was used as the control: the sterol synthesis was decreased by 49 +/- 4% without inhibiting the protein synthesis. A number of the cultures produced compounds inhibiting under the experimental conditions the synthesis of sterols by 70 to 80% with simultaneous inhibition of the protein synthesis at least by 60 to 70%. Three compounds from that group produced by streptomycetes were subjected to a more detailed investigation. The compounds were demonstrated to be active antifungal antibiotics (MIC 0.1-1 mcg/ml). In a dose of 0.1-1 mcg/ml they showed high immunosuppressive activity in models of lymphocyte transformation in mice, whereas cyclosporin was active in a dose of 1 mcg/ml. Therefore, the model for screening hypolipidemic compounds could be considered useful for screening promising natural immunosuppressors.
在利用放线菌和真菌筛选甾醇合成抑制剂的实验中，共检测了702株菌株。通过将3H醋酸盐掺入甾醇和蛋白质中，测定了真菌和放线菌菌丝体乙醇提取物在1/10(3)稀释度下对Hep G2肝癌细胞甾醇合成的影响。洛伐他汀（200 pg/ml）用作对照：甾醇合成降低了49±4%，而蛋白质合成未受抑制。许多培养物产生的化合物在实验条件下可使甾醇合成降低70%至80%，同时蛋白质合成至少抑制60%至70%。对链霉菌产生的该组中的三种化合物进行了更详细的研究。这些化合物被证明是活性抗真菌抗生素（最低抑菌浓度为0.1 - 1 mcg/ml）。在0.1 - 1 mcg/ml的剂量下，它们在小鼠淋巴细胞转化模型中显示出高免疫抑制活性，而环孢素在1 mcg/ml的剂量下才有活性。因此，用于筛选降血脂化合物的模型可被认为有助于筛选有前景的天然免疫抑制剂。
