Structural identification of Diindole agonists of the aryl hydrocarbon receptor derived from degradation of indole-3-pyruvic acid.
Structural identification of Diindole agonists of the aryl hydrocarbon receptor derived from degradation of indole-3-pyruvic acid.
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DOI：
10.1021/tx9000418
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发表时间：
2009-12
影响因子：
4.1
通讯作者：
Guengerich, F. Peter
中科院分区：
文献类型：
--
作者：
Chowdhury, Goutam;Dostalek, Miroslav;Hsu, Erin L.;Nguyen, Linh P.;Stec, Donald F.;Bradfield, Christopher A.;Guengerich, F. Peter
色氨酸转氨/氧化产物吲哚-3-丙酮酸 (I3P) 在 pH 7.4 和 37 °C 下有氧孵育，产生具有 Ah 受体 (AHR) 激动剂活性的产物。使用 HPLC 对提取物进行分级并筛选 AHR 激动剂活性。两种化合物被鉴定为激动剂：1,3-二(1H-吲哚-3-基)丙-2-酮 (1) 和 1-(1H-吲哚-3-基)-3-(3H-吲哚-3-亚基)丙-2-酮 (2)，其中 2 的效力为 100 倍 > 1（Chem. Res. Toxicol. 22, xxx-xxx，随附论文）。 1和2均显示出指示吲哚的UV光谱。通过高分辨率质谱（HRMS）建立了分子式，并通过结合NMR方法（包括1H、自然丰度13C和二维方法）确定了结构。 I3P 氧化成 1 的中间体是 3-羟基-2,4-二(1H-吲哚-3-基)丁醛（HRMS 证实存在式 C20H19N2O2 的化合物）。化合物1在空气中或（更快）用温和氧化剂转化为2，并且2可以进一步氧化为1,3-二(3H-吲哚-3-亚基)丙-2-酮。结构的确定可以估计这些天然产物的摩尔 Ah 受体激动剂活性，其效力与已知的经典 AHR 诱导剂相似。
Aerobic incubation of the tryptophan transamination/oxidation product indole-3-pyruvic acid (I3P) at pH 7.4 and 37 °C yielded products with activity as Ah receptor (AHR) agonists. The extracts were fractionated using HPLC and screened for AHR agonist activity. Two compounds were identified as agonists: 1,3-di(1H-indol-3-yl)propan-2-one (1) and 1-(1H-indol-3-yl)-3-(3H-indol-3-ylidene) propan-2-one (2), with the potency of 2 being 100-fold > 1 ( Chem. Res. Toxicol. 22, xxx-xxx, accompanying paper). Both 1 and 2 showed UV spectra indicative of indole. The molecular formulae were established by high-resolution mass spectrometry (HRMS) and the structures were determined by a combination of NMR methods, including 1H, natural abundance 13C, and two-dimensional methods. An intermediate in the oxidation of I3P to 1 is 3-hydroxy-2,4-di(1H-indol-3-yl)butanal (HRMS established the presence of a compound with the formula C20H19N2O2). Compound 1 was converted to 2 in air or (faster) with mild oxidants, and 2 could be further oxidized to 1,3-di(3H-indol-3-ylidene)propan-2-one. Determination of the structures allowed estimation of the molar Ah receptor agonist activity of these natural products, similar in potency to known classical AHR inducers.
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DOI：
10.1073/pnas.190256997
发表时间：
2000-09-12
影响因子：
11.1
作者：
Lahvis, GP;Lindell, SL;Bradfield, CA
通讯作者：
Bradfield, CA
DOI：
10.1073/pnas.88.21.9543
发表时间：
1991-11-01
影响因子：
11.1
作者：
BJELDANES, LF;KIM, JY;BRADFIELD, CA
通讯作者：
BRADFIELD, CA
影响因子：
4.1
作者：
Nguyen, Linh P.;Hsu, Erin L.;Bradfield, Christopher A.
通讯作者：
Bradfield, Christopher A.
影响因子：
6.9
作者：
JONES, A;GALSTON, AW
通讯作者：
GALSTON, AW
影响因子：
64.8
作者：
POLAND, A;PALEN, D;GLOVER, E
通讯作者：
GLOVER, E