Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics.
Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics.
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DOI：
10.1039/c3np70106a
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发表时间：
2014-07
影响因子：
11.9
通讯作者：
Bowers AA
中科院分区：
文献类型：
--
作者：
Li B;Wever WJ;Walsh CT;Bowers AA
二硫代吡咯酮 (DTP) 类抗生素在 20 世纪上半叶首次被分离出来，但直到最近，从这类结构有趣的分子的合成和生物合成中获得的见解才重新唤醒了研究。 DTP 的特点是具有独特的电子双环结构，其中包含两个烯硫醇之间的紧凑二硫桥。化合物类别内的多样性点出现在双环核心外部的两个酰胺氮处。这些修饰区分了该类中研究最深入的三种成员：全霉素、硫芦丁和金丝菌素。最近还在海洋抗生素 thiomarinol 中发现了 DTP 核心，其中它与 marinolic 酸部分相连，该部分是 FDA 批准的外用抗生素 Bactroban®（葛兰素史克）的类似物。二硫代吡咯酮对许多革兰氏阳性和革兰氏阴性细菌以及结核分枝杆菌菌株表现出相对广谱的抗生素活性。此外，它们已被证明具有有效和选择性的抗癌活性。尽管前景光明，但 DTP 的作用机制仍然有很多未知之处。早期报告表明，它们在转录水平上抑制酵母生长，这种效应在很大程度上是其独特的微生物静态特性的原因。细菌也支持类似的机制。阐明棒状链霉菌和鲁克耶尔森氏菌中的全霉素以及拉瓦交替单胞菌中的硫代马里诺的生物合成途径。十一月SANK 73390 提供的证据表明，多种机制可能在这些化合物的活性中发挥作用。本综述将全面介绍二硫代吡咯酮类化合物的历史和发展，特别重点关注其生物合成、合成、生物活性和作用机制。
Dithiolopyrrolone (DTP) group antibiotics were first isolated in the early half of the 20th century, but only recently has research been reawakened by insights gained from the synthesis and biosynthesis of this structurally intriguing class of molecules. DTPs are characterized by an electronically unique bicyclic structure, which contains a compact disulfide bridge between two ene-thiols. Points of diversity within the compound class occur outside of the bicyclic core, at the two amide nitrogens. Such modifications distinguish three of the most well studied members of the class, holomycin, thiolutin, and aureothricin; the DTP core has also more recently been identified in the marine antibiotic thiomarinol, in which it is linked to a marinolic acid moiety, analog of the FDA-approved topical antibiotic Bactroban® (GlaxoSmithKline). Dithiolopyrrolones exhibit relatively broad-spectrum antibiotic activity against many Gram-positive and Gram-negative bacteria, as well as strains of Mycobacterium tuberculosis. Additionally, they have been shown to exhibit potent and selective anti-cancer activity. Despite this promising profile, there is still much unknown about the mechanisms of action for DTPs. Early reports suggested that they inhibit yeast growth at the level of transcription and that this effect is largely responsible for their distinctive microbial static properties; a similar mechanism is supported in bacteria. Elucidation of biosynthetic pathways for holomycin in Streptomyces clavuligerus and Yersinia ruckeri and thiomarinol in Alteromonas rava sp. nov. SANK 73390, have contributed evidence suggesting that multiple mechanisms may be operative in the activity of these compounds. This review will comprehensively cover the history and development of dithiolopyrrolones with particular emphasis on the biosynthesis, synthesis, biological activity and mechanism of action.
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影响因子：
3.6
作者：
ELLIS, JE;FRIED, JH;ROSS, CH
通讯作者：
ROSS, CH
影响因子：
15
作者：
Forseth, Ry R.;Fox, Ellen M.;Chung, DaWoon;Howlett, Barbara J.;Keller, Nancy P.;Schroeder, Frank C.
通讯作者：
Schroeder, Frank C.
影响因子：
5.3
作者：
Das, B;Butler, JS;Sherman, F
通讯作者：
Sherman, F
影响因子：
3.2
作者：
Hjelmgaard, Thomas;Givskov, Michael;Nielsen, John
通讯作者：
Nielsen, John
影响因子：
4.4
作者：
JUHL, MJ;CLARK, DP
通讯作者：
CLARK, DP