琥珀酸氢化可的松与紫斑门氏菌和棘皮莞氏菌全细胞培养物的生物转化

IF 2.1 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Steroids Pub Date : 2024-06-30 DOI:10.1016/j.steroids.2024.109466
Abdur Rahman Khan , Zainab Aziz , Amir Iqbal , Sheema , Afsana Rashid Khan , Salman Zafar
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引用次数: 0

摘要

琥珀酸氢化可的松(1)是一种合成消炎药,也是合成其他类固醇药物的关键中间体。本研究利用紫云英菌(Monascus purpureus)和棘菌(Cunninghamella echinulata)菌株对 1 进行真菌生物转化。通过侧链裂解、水解、脱氢和氧化反应,化合物 1 被转化为四种代谢物,分别为氢化可的松(2)、11β-羟基雄甾-4-烯-3,17-二酮(3)、Δ1-木栓酸(4)和氢化可的松-17-琥珀酸酯(5)。这些化合物以前都是由不同的前体通过化学或酶法合成的。虽然这不是第一份关于 1 的生物转化的报告,但显然是第一份借助现代光谱技术对化合物 1 的生物转化产物进行结构表征的报告。值得注意的是,这些产物已经显示出了生物潜力,然而,对这些代谢产物的抗炎特性进行更深入的研究将具有很高的价值。这些结果不仅强调了生物转化在催化反应方面的巨大潜力,否则化学反应是无法实现的,而且也为开发新型抗炎化合物带来了希望。
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Biotransformation of hydrocortisone succinate with whole cell cultures of Monascus purpureus and Cunninghamella echinulata

Hydrocortisone succinate (1) is a synthetic anti-inflammatory drug and key intermediate in the synthesis of other steroidal drugs. This work is based on the fungal biotransformation of 1, using Monascus purpureus and Cunninghamella echinulata strains. Comopound 1 was transformed into four metabolites, identified as hydrocortisone (2), 11β-hydroxyandrost-4-en-3,17-dione (3), Δ1-cortienic acid (4), and hydrocortisone-17-succinate (5), obtained through side chain cleavage, hydrolysis, dehydrogenation, and oxidation reactions. These compounds have previously been synthesized either chemically or enzymatically from different precursors. Though this is not the first report on the biotransformation of 1, but it obviously is a first, where the biotransformed products of compound 1 have been characterized structurally with the help of modern spectroscopic techniques. It is noteworthy that these products have already shown biological potential, however a more thorough investigation of the anti-inflammatory properties of these metabolites would be of high value. These results not only emphasize upon the immense potential of biotransformation in catalysis of reactions, otherwise not-achievable chemically, but also holds promise for the development of novel anti-inflammatory compounds.

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来源期刊
Steroids
Steroids 医学-内分泌学与代谢
CiteScore
5.10
自引率
3.70%
发文量
120
审稿时长
73 days
期刊介绍: STEROIDS is an international research journal devoted to studies on all chemical and biological aspects of steroidal moieties. The journal focuses on both experimental and theoretical studies on the biology, chemistry, biosynthesis, metabolism, molecular biology, physiology and pharmacology of steroids and other molecules that target or regulate steroid receptors. Manuscripts presenting clinical research related to steroids, steroid drug development, comparative endocrinology of steroid hormones, investigations on the mechanism of steroid action and steroid chemistry are all appropriate for submission for peer review. STEROIDS publishes both original research and timely reviews. For details concerning the preparation of manuscripts see Instructions to Authors, which is published in each issue of the journal.
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