Human health benefits from consuming cruciferous vegetables that release indole-3-carbinol (I3C), but the in vivo transformation of I3C-related indoles remains underinvestigated. Here we present the post-ingestion conversion of I3C into antitumor agents, 2-(indol-3-ylmethyl)-3,3′-diindolylmethane (LTr1) and 3,3′-diindolylmethane (DIM), by conceptualizing and materializing the reaction flux derailing (RFD) approach as a means of unraveling these stepwise transformations to be non-enzymatic but pH-dependent and gut microbe-sensitive. In the upper (or acidic) gastrointestine, LTr1 generates through the Michael addition of 3-methyleneindolium (3MI, derived in situ from I3C) to DIM producing from I3C via the formaldehyde-releasing (major) and CO2-liberating (minor) pathways. In the large intestine, ‘endogenous’ I3C and DIM can form respectively from couplings of formaldehyde with one and two molecules of indole (a tryptophan catabolite). Acid-producing gut bacteria such as Lactobacillus acidophilus facilitate the H+-promotable steps. The work updates the understanding on the merits of I3C consumptions and identifies LTr1 as a drug candidate.

中文翻译：

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摄入后将膳食吲哚转化为抗癌剂

食用释放吲哚-3-甲醇 (I3C) 的十字花科蔬菜对人类健康有益，但 I3C 相关吲哚的体内转化仍未得到充分研究。在这里，我们通过概念化和具体化反应，展示了 I3C 摄入后转化为抗肿瘤剂 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1) 和 3,3'-diindolylmethane (DIM)通量脱轨（RFD）方法作为解开这些逐步转化为非酶促但pH依赖性和肠道微生物敏感的一种手段。在上部（或酸性）胃肠道中，LTr1 通过迈克尔加成 3-亚甲基吲哚（3MI，从 I3C 原位衍生）到通过甲醛释放（主要）和 CO2 释放（次要）途径从 I3C 产生的 DIM 中生成。在大肠里，“内源性”I3C 和 DIM 可以分别由甲醛与一个和两个吲哚分子（一种色氨酸分解代谢物）的偶联形成。产酸肠道细菌如嗜酸乳杆菌促进 H+ 促进步骤。这项工作更新了对 I3C 消耗优点的理解，并将 LTr1 确定为候选药物。