Beta-Carboline


β-Carboline, also known as norharmane, is a nitrogen containing heterocycle. It is also the prototype of a class of indole alkaloid compounds known as β-carbolines.

Pharmacology

β-Carboline alkaloids are widespread in plants and animals, and frequently act as GABAA inverse agonists. As components of the liana Banisteriopsis caapi, the β-carbolines harmine, harmaline, and tetrahydroharmine play a pivotal role in the pharmacology of the indigenous psychedelic drug ayahuasca by preventing the breakdown of dimethyltryptamine in the gut by reversibly inhibiting monoamine oxidase, thus making it psychoactive upon oral administration. Some β-carbolines, notably tryptoline and pinoline, may be formed naturally in the human body. The latter is possibly implicated along with melatonin in the role of the pineal gland in regulating the sleep-wake cycle. β-carboline is a GABAA benzodiazepine site inverse agonist and can therefore have convulsive, anxiogenic and memory enhancing effects. 3-hydroxymethyl-beta-carboline blocks the sleep-promoting effect of flurazepam in rodents, and by itself can decrease sleep in a dose-dependent manner. 9-Methyl-β-carbolines appear to induce DNA damage when exposed to ultra-violet light.

Structure

β-Carboline belongs to the group of indole alkaloids and consist of pyridine ring that is fused to an indole skeleton. The structure of β-carboline is similar to that of tryptamine, with the ethylamine chain re-connected to the indole ring via an extra carbon atom, to produce a three-ringed structure. The biosynthesis of β-carbolines is believed to follow this route from analogous tryptamines. Different levels of saturation are possible in the third ring, which is indicated here in the structural formula by colouring the optionally double bonds red and blue:

Examples of β-carbolines

Some of the more important β-carbolines are tabulated by structure below. Their structures may contain the aforementioned bonds marked by red or blue.
Short Name
Red Bond
Blue Bond
R1R6R7R9Structure
β-Carboline
×
×
H
H
H
H
Tryptoline
H
H
H
H
Pinoline
H
OCH3
H
H
Harmane
×
×
CH3
H
H
H
Harmine
×
×
CH3
H
OCH3
H
Harmaline
×
CH3
H
OCH3
H
Tetrahydroharmine
CH3
H
OCH3
H
9-Methyl-β-carboline
×
×
H
H
H
CH3

Occurrence in nature

Eight plant families are known to express 64 different kinds of β-carboline alkaloids. By dry weight, the seeds of Peganum harmala contain between 0.16% and 5.9% β-carboline alkaloids.
As a result of the presence of β-carbolines in the cuticle of scorpions, their skin is known to fluoresce when exposed to certain wavelengths of ultraviolet light such as that produced by a blacklight.
A group of β-carboline derivatives, termed eudistomins were extracted from ascidians, like Ritterella sigillinoides, Lissoclinum fragile or Pseudodistoma aureum. Nostocarboline was isolated from freshwater cyanobacterium.
β-carboline derivatives are known to induce the production of secondary metabolite in various soil dwelling “Streptomyces” species. Defined as biomediator, these molecules are known to enhance the expression of secondary metabolite biosynthetic genes by binding to Large ATP-binding regulator of the LuxR family.