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来源于 sp. PAMC 23288 的葡萄糖基转移酶的合成代谢类固醇糖苷的酶促合成。

Enzymatic Synthesis of Anabolic Steroid Glycosides by Glucosyltransferase from sp. PAMC 23288.

机构信息

Department of Life Science and Biochemical Engineering, SunMoon University, Asan 31460, Republic of Korea.

Department of Pharmaceutical Engineering and Biotechnology, SunMoon University, Asan 31460, Republic of Korea.

出版信息

J Microbiol Biotechnol. 2020 Apr 28;30(4):604-614. doi: 10.4014/jmb.1911.11057.

Abstract

The application of steroids has steadily increased thanks to their therapeutic effects. However, alternatives are required due their severe side effects; thus, studies on the activities of steroid derivatives are underway. Sugar derivatives of nandrolone, which is used to treat breast cancer, as well as cortisone and prednisone, which reduce inflammation, pain, and edema, are unknown. We linked O-glucose to nandrolone and testosterone using UDP-glucosyltransferase (UGT-1) and, then, tested their bioactivities in vitro. Analysis by NMR showed that the derivatives were 17β-nandrolone β-D-glucose and 17β-testosterone β-D-glucose, respectively. The viability was higher and cytotoxicity was evident in PC12 cells incubated with rotenone and, testosterone derivatives, compared to the controls. SH-SY5Y cells incubated with HO and nandrolone derivatives remained viable and cytotoxicity was attenuated. Both derivatives enhanced neuronal protective effects and increased the amounts of cellular ATP.

摘要

由于类固醇的治疗效果,其应用稳步增加。然而,由于其严重的副作用,需要替代品;因此,正在对类固醇衍生物的活性进行研究。目前还不知道用于治疗乳腺癌的那屈醇和可减轻炎症、疼痛和水肿的可的松和泼尼松的糖衍生物。我们使用 UDP-葡萄糖基转移酶 (UGT-1) 将 O-葡萄糖与那屈醇和睾酮连接起来,然后在体外测试它们的生物活性。NMR 分析表明,衍生物分别为 17β-那屈醇β-D-葡萄糖和 17β-睾酮β-D-葡萄糖。与对照组相比,与鱼藤酮和睾酮衍生物孵育的 PC12 细胞活力更高,细胞毒性更明显。与 HO 和那屈醇衍生物孵育的 SH-SY5Y 细胞保持活力,细胞毒性减弱。两种衍生物均增强了神经元保护作用并增加了细胞内 ATP 的含量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f6b/9728329/05115cc1fe6e/JMB-30-4-604-f1.jpg

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