Indoles are widely distributed in nature, most notably as amino acid tryptophan and neurotransmitter serotonin.

[5] When indole is a substituent on a larger molecule, it is called an indolyl group by systematic nomenclature.

Substituted indoles are structural elements of (and for some compounds, the synthetic precursors for) the tryptophan-derived tryptamine alkaloids, which includes the neurotransmitter serotonin and the hormone[6] melatonin, as well as the naturally occurring psychedelic drugs dimethyltryptamine and psilocybin.

Other indolic compounds include the plant hormone auxin (indolyl-3-acetic acid, IAA), tryptophol, the anti-inflammatory drug indomethacin, and the betablocker pindolol.

[11] A number of indole derivatives have important cellular functions, including neurotransmitters such as serotonin.

[2] Common classical methods applied for the detection of extracellular and environmental indoles, are Salkowski, Kovács, Ehrlich’s reagent assays and HPLC.

[16][17][18] For intracellular indole detection and measurement genetically encoded indole-responsive biosensor is applicable.

[19] Indoles and their derivatives are promising against tuberculosis, malaria, diabetes, cancer, migraines, convulsions, hypertension, bacterial infections of methicillin-resistant Staphylococcus aureus (MRSA) and even viruses.

[30] Unlike most amines, indole is not basic: just like pyrrole, the aromatic character of the ring means that the lone pair of electrons on the nitrogen atom is not available for protonation.

Indole is primarily protonated at the C3, rather than N1, owing to the enamine-like reactivity of the portion of the molecule located outside of the benzene ring.

A noteworthy exception occurs when electrophilic substitution is carried out in conditions sufficiently acidic to exhaustively protonate C3.

[35] Gramine, a useful synthetic intermediate, is produced via a Mannich reaction of indole with dimethylamine and formaldehyde.

The N–H center has a pKa of 21 in DMSO, so that very strong bases such as sodium hydride or n-butyl lithium and water-free conditions are required for complete deprotonation.

[40][41][42][43] One example is the Pictet-Spengler reaction between tryptophan derivatives and aldehydes,[44] which produces a mixture of diastereomers, leading to reduced yield of the desired product.