3-Indolepropionic acid

Description

3-Indolepropionic acid is a bacterial metabolite that has antioxidant and neuroprotective activities. It scavenges ABTS radicals in a cell-free assay when used at concentrations ranging from 50 to 150 μM and decreases hydrogen peroxide-induced malondialdehyde (MDA) levels in rat striatal membranes (IC₅₀ = 180 μM). Indole-3-propionic acid also decreases increases in MDA levels induced by amyloid β (1-42) in PC12 cells. It decreases ischemia-induced increases in cell death of pyramidal neurons and levels of 4-hydroxy nonenal (HNE; ) and glial fibrillary acidic protein (GFAP) in the hippocampal CA1 region in gerbils when administered at a dose of 10 mg/kg per day.

Chemical Properties

pale yellow to yellow crystalline powder

Uses

3-Indolepropionic acid is a deamination product of Tryptophan (T947200) that protects the hippocampus (studied in gerbils) from ischemic damage and oxidative stress. It’s ability to protect the neurons in this way is attributed to its potent antioxidative effects. 3-Indolepropionic acid is also hypothesized to have protective effects on the thyroid gland.

Uses

Reactant for preparation of:

• Fluorescent analogues of strigolactones
• Anti-tumor agents
• Melanocortin receptors ligands
• Immunosuppressive agents
• Iinhibitors of hepatitis C virus
• Histamine H4 receptor agonists
• NR2B/NMDA receptor antagonists
• CB1 antagonist for the treatment of obesity
• Antibacterial agents
• Inhibitor of TGF-β receptor binding

Definition

ChEBI: An indol-3-yl carboxylic acid that is propionic acid substituted by a 1H-indol-3-yl group at position 3.

Synthesis Reference(s)

Tetrahedron Letters, 25, p. 3159, 1984 DOI: 10.1016/S0040-4039(01)90997-9

General Description

3-Indolepropionic acid is an effective inhibitor of aggregation of misfolded β-amyloid protein (Abeta). Three-component one-pot procedure has been reported to assemble 3-indolepropionic acids.

Biochem/physiol Actions

Studied as an adjunct to improve perfusion after liver transplant.

Synthesis

3-Indolepropionic acid is mainly prepared by reacting indole with acrylic acid and acetic anhydride under heating and stirring conditions, first generating an intermediate of acetyl indole-3-propionic acid. Subsequently, this ester intermediate is subjected to alkaline hydrolysis (e.g., using an aqueous sodium hydroxide solution) to remove the acetyl group and hydrolyze the ester bond. Finally, an acidification step yields the target product, 3-indolepropionic acid.

Purification Methods

Recrystallise it from EtOH/water [James & Ware J Phys Chem 89 5450 1985]. The picrate has m 143-144o, and the methyl ester crystallises from *C6H6 or MeOH with m 81-83o. [Beilstein 22 III/IV 1113, 22/3 V 114.]

References

[1] WILLIAM R WIKOFF. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 10: 3698-3703. DOI: 10.1073/pnas.0812874106
[2] BURKHARD POEGGELER . Indole-3-propionate: a potent hydroxyl radical scavenger in rat brain[J]. Brain Research, 1999, 815 2: Pages 382-388. DOI: 10.1016/s0006-8993(98)01027-0
[3] IN KOO HWANG. Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus[J]. Journal of Neuroscience Research, 2009, 87 9: 2126-2137. DOI: 10.1002/jnr.22030
[4] Y J CHYAN. Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid.[J]. The Journal of Biological Chemistry, 1999, 274 31: 21937-21942. DOI: 10.1074/jbc.274.31.21937