TY - JOUR
T1 - Indole scaffolds as a promising class of the aryl hydrocarbon receptor ligands
AU - Dvořák, Zdeněk
AU - Poulíková, Karolína
AU - Mani, Sridhar
N1 - Publisher Copyright:
© 2021 Elsevier Masson SAS
PY - 2021/4/5
Y1 - 2021/4/5
N2 - 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.
AB - 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.
KW - Aryl hydrocarbon receptor
KW - Indoles
KW - Ligands
KW - Rational design
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U2 - 10.1016/j.ejmech.2021.113231
DO - 10.1016/j.ejmech.2021.113231
M3 - Review article
C2 - 33582577
AN - SCOPUS:85100737615
SN - 0223-5234
VL - 215
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
M1 - 113231
ER -