Indole-3-carbaldehyde

Indole-3-carbaldehyde (I3A), also known as indole-3-aldehyde and 3-formylindole, is a metabolite of dietary L-tryptophan which is synthesized by human gastrointestinal bacteria, particularly species of the Lactobacillus genus.^[2][3] I3A is a biologically active metabolite which acts as a receptor agonist at the aryl hydrocarbon receptor in intestinal immune cells, in turn stimulating the production of interleukin-22 which facilitates mucosal reactivity.^[4][3][2]

Indole-3-carbaldehyde

Names
IUPAC name 1H-Indole-3-carbaldehyde
Other names 3-Formylindole; Indole-3-carboxaldehyde; Indole-3-aldehyde
Identifiers
CAS Number	487-89-8
3D model (JSmol)	Interactive image
Beilstein Reference	5-21-08-00246
ChEMBL	ChEMBL147741
ChemSpider	9838
ECHA InfoCard	100.006.969
EC Number	207-665-8
PubChem CID	10256
UNII	7FN04C32UO
CompTox Dashboard (EPA)	DTXSID5060069
InChI InChI=1S/C9H7NO/c11-6-7-5-10-9-4-2-1-3-8(7)9/h1-6,10H Key: OLNJUISKUQQNIM-UHFFFAOYSA-N
SMILES C1=CC=C2C(=C1)C(=CN2)C=O
Properties
Chemical formula	C9H7NO
Molar mass	145.161 g·mol−1
Melting point	198 °C (388 °F; 471 K)
Structure
Crystal structure	Orthorhombic
Space group	Pca21
Lattice constant	a = 14.076, b = 5.8059, c = 8.6909[1]
Lattice volume (V)	710.3
Formula units (Z)	4
Hazards
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H315, H319, H335
Precautionary statements	P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Biosynthesis in humans and cellular effects

Tryptophan metabolism by human gut microbiota ( v t e ) Tryptophan Clostridium sporogenes Lacto- bacilli Tryptophanase- expressing bacteria IPA I3A Indole Liver Brain IPA I3A Indole Indoxyl sulfate AST-120 AhR Intestinal immune cells Intestinal epithelium PXR Mucosal homeostasis: ↓TNF-α ↑Junction protein- coding mRNAs L cell GLP-1 T J Neuroprotectant: ↓Activation of glial cells and astrocytes ↓4-Hydroxy-2-nonenal levels ↓DNA damage –Antioxidant –Inhibits β-amyloid fibril formation Maintains mucosal reactivity: ↑IL-22 production Associated with vascular disease: ↑Oxidative stress ↑Smooth muscle cell proliferation ↑Aortic wall thickness and calcification Associated with chronic kidney disease: ↑Renal dysfunction –Uremic toxin Kidneys This diagram shows the biosynthesis of bioactive compounds (indole and certain other derivatives) from tryptophan by bacteria in the gut.[2] Indole is produced from tryptophan by bacteria that express tryptophanase.[2] Clostridium sporogenes metabolizes tryptophan into indole and subsequently 3-indolepropionic acid (IPA),[5] a highly potent neuroprotective antioxidant that scavenges hydroxyl radicals.[2][6][7] IPA binds to the pregnane X receptor (PXR) in intestinal cells, thereby facilitating mucosal homeostasis and barrier function.[2] Following absorption from the intestine and distribution to the brain, IPA confers a neuroprotective effect against cerebral ischemia and Alzheimer's disease.[2] Lactobacillaceae (Lactobacillus s.l.) species metabolize tryptophan into indole-3-aldehyde (I3A) which acts on the aryl hydrocarbon receptor (AhR) in intestinal immune cells, in turn increasing interleukin-22 (IL-22) production.[2] Indole itself triggers the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells and acts as a ligand for AhR.[2] Indole can also be metabolized by the liver into indoxyl sulfate, a compound that is toxic in high concentrations and associated with vascular disease and renal dysfunction.[2] AST-120 (activated charcoal), an intestinal sorbent that is taken by mouth, adsorbs indole, in turn decreasing the concentration of indoxyl sulfate in blood plasma.[2]

Chemistry

Indole-3-carbaldehyde has reactivity typical of aromatic aldehydes. It can is easily oxidized to indole-3-carboxylic acid. It condenses with nitromethane in a Henry reaction to give 3-nitrovinyl indole.

Antifungal properties

Indole-3-carbaldehyde has antifungal properties, and partially accounts for the protection from chytridiomycosis seen in amphibian species which carry Janthinobacterium lividum on their skin.^[8]