Indole scaffolds as a promising class of the aryl hydrocarbon receptor ligands

被引:37
作者
Dvorak, Zdenek [1 ]
Poulikova, Karolina [1 ]
Mani, Sridhar [2 ]
机构
[1] Palacky Univ, Fac Sci, Dept Cell Biol & Genet, Slechtitelu 27, Olomouc 78371, Czech Republic
[2] Albert Einstein Coll Med, Dept Med & Genet, Bronx, NY 10461 USA
关键词
Aryl hydrocarbon receptor; Ligands; Indoles; Rational design; AH RECEPTOR; KINASE INHIBITOR; DIOXIN RECEPTOR; IN-VIVO; ACTIVATION; TRYPTOPHAN; AGONIST; MODULATION; EXPRESSION; INDUCTION;
D O I
10.1016/j.ejmech.2021.113231
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The aryl hydrocarbon receptor (AhR), deemed initially as a xenobiotic sensor, plays multiple physiological roles and is involved in various pathophysiological processes and many diseases' etiology. Therefore, the therapeutic and chemopreventive targeting of AhR is a fundamental issue. To date, thousands of structurally diverse ligands of AhR have been identified. The bottleneck in targeting the AhR is that it is a Janus-faced player with beneficial vs. harmful effects in the ligand-specific context. A distinct structural class of the AhR ligands is those with indole-based scaffolds. The present review summarizes the knowledge on the existing indole-derived AhR ligands, comprising natural and dietary compounds, synthetic compounds including clinically used drugs, endogenous intermediary metabolites, and catabolites produced by human microbiota. The examples of novel, indole ring containing, rational design based AhR ligands are presented. The molecular, in vitro, and in vivo effects are described. (C) 2021 Elsevier Masson SAS. All rights reserved.
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页数:10
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共 89 条
  • [1] Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine
    Adachi, J
    Mori, Y
    Matsui, S
    Takigami, H
    Fujino, J
    Kitagawa, H
    Miller, CA
    Kato, T
    Saeki, K
    Matsuda, T
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (34) : 31475 - 31478
  • [2] The aryl hydrocarbon receptor (AhR) as a breast cancer drug target
    Baker, Jennifer R.
    Sakoff, Jennette A.
    McCluskey, Adam
    [J]. MEDICINAL RESEARCH REVIEWS, 2020, 40 (03) : 972 - 1001
  • [3] Aspartate aminotransferase generates proagonists of the aryl hydrocarbon receptor
    Bittinger, MA
    Nguyen, LP
    Bradfield, CA
    [J]. MOLECULAR PHARMACOLOGY, 2003, 64 (03) : 550 - 556
  • [4] AROMATIC HYDROCARBON RESPONSIVENESS-RECEPTOR AGONISTS GENERATED FROM INDOLE-3-CARBINOL INVITRO AND INVIVO - COMPARISONS WITH 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN
    BJELDANES, LF
    KIM, JY
    GROSE, KR
    BARTHOLOMEW, JC
    BRADFIELD, CA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (21) : 9543 - 9547
  • [5] Aryl Hydrocarbon Receptor Antagonists Promote the Expansion of Human Hematopoietic Stem Cells
    Boitano, Anthony E.
    Wang, Jian
    Romeo, Russell
    Bouchez, Laure C.
    Parker, Albert E.
    Sutton, Sue E.
    Walker, John R.
    Flaveny, Colin A.
    Perdew, Gary H.
    Denison, Michael S.
    Schultz, Peter G.
    Cooke, Michael P.
    [J]. SCIENCE, 2010, 329 (5997) : 1345 - 1348
  • [6] Modulation of cytochrome P-450 and glutathione S-transferase isoform expression in vivo by intact and degraded indolyl glucosinolates
    Bonnesen, C
    Stephensen, PU
    Andersen, O
    Sorensen, H
    Vang, O
    [J]. NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 1999, 33 (02): : 178 - 187
  • [7] Acyl glucuronide reactivity in perspective
    Bradshaw, Peter R.
    Athersuch, Toby J.
    Stachulski, Andrew, V
    Wilson, Ian D.
    [J]. DRUG DISCOVERY TODAY, 2020, 25 (09) : 1639 - 1650
  • [8] The Glycogen Synthase Kinase Inhibitor 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763) Is a Partial Agonist of the Aryl Hydrocarbon Receptor
    Braeuning, Albert
    Buchmann, Albrecht
    [J]. DRUG METABOLISM AND DISPOSITION, 2009, 37 (08) : 1576 - 1580
  • [9] Analysis of Glycogen Synthase Kinase Inhibitors That Regulate Cytochrome P450 Expression in Primary Human Hepatocytes by Activation of β-Catenin, Aryl Hydrocarbon Receptor and Pregnane X Receptor Signaling
    Briolotti, Philippe
    Chaloin, Laurent
    Balaguer, Patrick
    Da Silva, Franck
    Tomankova, Veronika
    Pascussi, Jean-Marc
    Duret, Cedric
    Fabre, Jean-Michel
    Ramos, Jeanne
    Klieber, Sylvie
    Maurel, Patrick
    Daujat-Chavanieu, Martine
    Gerbal-Chaloin, Sabine
    [J]. TOXICOLOGICAL SCIENCES, 2015, 148 (01) : 261 - 275
  • [10] Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells
    Chen, I
    Safe, S
    Bjeldanes, L
    [J]. BIOCHEMICAL PHARMACOLOGY, 1996, 51 (08) : 1069 - 1076