Department of Life Sciences and Biotechnology, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy.
GATE SRL, Via L. Borsari, 46, 44121 Ferrara, Italy.
Molecules. 2020 May 7;25(9):2192. doi: 10.3390/molecules25092192.
Prednisone and prednisolone are steroids widely used as anti-inflammatory drugs. Development of the pharmaceutical industry is currently aimed at introducing biotechnological processes and replacing multiple-stage chemical syntheses. In this work we evaluated the ability of bacteria belonging to the genus to biotransform substrates, such as cortisone and hydrocortisone, to obtain prednisone and prednisolone, respectively. These products are of great interest from a pharmaceutical point of view as they have higher anti-inflammatory activity than the starting substrates. After an initial lab-scale screening of 13 strains, to select the highest producers of prednisone and prednisolone, we reported the 200 ml-batch scale-up to test the process efficiency and productivity of the most promising strains. , and gave the Δ1-dehydrogenation products of cortisone and hydrocortisone (prednisone and prednisolone) in variable amounts. In these biotransformations, the formation of products with the reduced carbonyl group in position C of the lateral chain of the steroid nucleus was also observed (i.e., 20β-hydroxy-prednisone and 20β-hydroxy-prednisolone). The yields, the absence of collateral products, and in some cases the absence of starting products allow us to say that cortisone and hydrocortisone are partly degraded.
泼尼松龙和泼尼松是广泛用作抗炎药物的类固醇。制药行业的发展目前旨在引入生物技术工艺,并取代多阶段化学合成。在这项工作中,我们评估了属于 的细菌转化底物(如可的松和氢化可的松)的能力,分别获得泼尼松龙和泼尼松。从药学角度来看,这些产品具有很高的兴趣,因为它们具有比起始底物更高的抗炎活性。在对 13 株菌进行初步实验室规模筛选以选择最高产泼尼松龙和泼尼松的菌后,我们报告了 200ml 分批扩大规模试验,以测试最有前途的菌的工艺效率和生产力。、 和 以可变量产生可的松和氢化可的松(泼尼松龙和泼尼松)的 Δ1-脱氢产物。在这些生物转化中,还观察到甾体核侧链 C 位羰基基团还原产物的形成(即 20β-羟基-泼尼松龙和 20β-羟基-泼尼松)。产率、不存在副产物,并且在某些情况下不存在起始产物,这使我们能够说可的松和氢化可的松部分降解。