β-Carboline

Source: Wikipedia, the free encyclopedia.
(Redirected from
Beta carboline
)


β-Carboline
Chemical structure of β-carboline
Names
Preferred IUPAC name
9H-Pyrido[3,4-b]indole
Other names
  • Norharmane
  • Norharman
  • 9H-β-Carboline
Identifiers
3D model (
JSmol
)
128414
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.005.418 Edit this at Wikidata
EC Number
  • 205-959-0
IUPHAR/BPS
KEGG
MeSH norharman
UNII
  • InChI=1S/C11H8N2/c1-2-4-10-8(3-1)9-5-6-12-7-11(9)13-10/h1-7,13H checkY
    Key: AIFRHYZBTHREPW-UHFFFAOYSA-N checkY
  • InChI=1/C11H8N2/c1-2-4-10-8(3-1)9-5-6-12-7-11(9)13-10/h1-7,13H
    Key: AIFRHYZBTHREPW-UHFFFAOYAG
  • c1ccc3c(c1)[nH]c2cnccc23
Properties
C11H8N2
Molar mass 168.20 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

β-Carboline (9H-

brain functions but can also exhibit antioxidant[1] effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective,[2] cognitive enhancing and anti-cancer properties.[3]

Pharmacology

The pharmacological effects of specific β-carbolines are dependent on their

noradrenaline.[8][9]

A synthetic

neurodegenerative processes.[11]

However, β-carbolines with substituents in position 3 reduce the effect of benzodiazepine on GABA-A receptors and can therefore have convulsive, anxiogenic and memory enhancing effects.[15] Moreover, 3-hydroxymethyl-beta-carboline blocks the sleep-promoting effect of flurazepam in rodents and - by itself - can decrease sleep in a dose-dependent manner.[16] Another derivative, methyl-β-carboline-3-carboxylate, stimulates learning and memory at low doses but can promote anxiety and convulsions at high doses.[15] With modification in position 9 similar positive effects have been observed for learning and memory without promotion of anxiety or convulsion.[12]

β-carboline derivatives also enhance the production of the antibiotic reveromycin A in soil dwelling "Streptomyces" species.[17][18] Specifically, expression of biosynthetic genes is facilitated by binding of the β-carboline to a large ATP-binding regulator of the LuxR family.

Also Lactobacillus spp. secretes a β-carboline (1-acetyl-β-carboline) preventing the pathogenic fungus Candida albicans to change to a more virulent growth form (yeast-to-filament transition). Thereby, β-carboline reverses imbalances in the microbiome composition causing pathologies ranging from vaginal candidiasis to fungal sepsis.[19]

Since β-carbolines also interact with various cancer-related molecules such as DNA, enzymes (GPX4, kinases, etc.) and proteins (ABCG2/BRCP1, etc.), they are also discussed as potential anticancer agents.[3]

Explorative human studies for the medical use of β-carbolines

The extract of the

antagonizes N-methyl-d-aspartate (NMDA) receptors,[26] some researchers speculatively attributed the rapid improvement in patients with Parkinson's disease to these antiglutamatergic effects.[20] However, the advent of synthetic anticholinergic drugs at that time led to the total abandonment of harmine.[20]

Structure

β-Carbolines belong to the group of

indole alkaloids and consist of a pyridine ring that is fused to an indole skeleton.[27] 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.[28] Different levels of saturation are possible in the third ring which is indicated here in the structural formula
by coloring the optionally double bonds red and blue:

Substituted beta-carbolines (structural formula)
Substituted beta-carbolines (structural formula)

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 R1 R6 R7 R9 Structure
β-Carboline H H H H β-Carboline
Pinoline H
OCH3
 H H Pinoline
Harmane
CH3
 H H H Harmane
Harmine
CH3
 H
OCH3
 H Harmine
Harmaline
CH3
 H
OCH3
 H Harmaline
Harmalol
CH3
 H OH H Harmalol
Tetrahydroharmine
CH3
 H
OCH3
 H Tetrahydroharmine
9-Methyl-β-carboline H H H
CH3
 9-Me-BC
3-Carboxy-Tetrahydrononharman H / CH3 / COOH H H H

Natural occurrence

A Paruroctonus scorpion fluorescing under a blacklight

β-Carboline alkaloids are widespread in prokaryotes, plants and animals. Some β-carbolines, notably tetrahydro-β-carbolines, may be formed naturally in plants and the human body with tryptophan, serotonin and tryptamine as precursors.

  • Altogether, eight plant families are known to express 64 different kinds of β-carboline alkaloids. For example, the β-carbolines harmine, harmaline, and tetrahydroharmine are components of the liana Banisteriopsis caapi and play a pivotal role in the pharmacology of the indigenous psychedelic drug ayahuasca. Moreover, the seeds of Peganum harmala (Syrian Rue) contain between 0.16%[29] and 5.9%[30] β-carboline alkaloids (by dry weight).
  • A specific group of β-carboline derivatives, termed
    tunicates of the family Ascidiacea) such as Ritterella sigillinoides,[31] Lissoclinum fragile [32] or Pseudodistoma aureum.[33]
  • cyanobacterium.[34]
  • The fully aromatic β-carbolines also occur in many foodstuffs, however in lower concentrations. The highest amounts have been detected in brewed coffee, raisins, well done fish and meats.[35] Smoking is another source of fully aromatic β-carbolines with levels up to thousands of µg per smoker each day.[36]
  • β-Carbolines have also been found in the
    blacklight).[37]

See also

References

  1. PMID 21485291
    .
  2. S2CID 205624339
    .
  3. ^
    S2CID 232159513
    .
  4. PMID 25250831
    .
  5. S2CID 27837814
    .
  6. PMID 10940539
    .
  7. ^
    S2CID 207408868
    .
  8. ^
    S2CID 21595062
    .
  9. PMID 19442174
    .
  10. S2CID 28551023
    .
  11. ^
    S2CID 16729205
    .
  12. ^
    S2CID 8832937
    .
  13. S2CID 24226033
    .
  14. S2CID 24899640
    .
  15. ^
    PMID 17334612
    .
  16. S2CID 43038332
    .
  17. PMID 30967594
    .
  18. PMID 32576869
    .
  19. PMID 34686660
    .
  20. ^
    PMID 30713897
    .
  21. PMID 15641199
    .
  22. S2CID 28243440
    .
  23. S2CID 40115950
    .
  24. PMID 19879939
    .
  25. PMID 24922073
    .
  26. S2CID 10309111
    .
  27. ^ The Encyclopedia of Psychoactive Plants: Ethnopharmacology and its Applications. Ratsch, Christian. Park Street Press c. 2005
  28. PMID 22043251
    .
  29. PMID 17723604
    .
  30. PMID 20036304
    .
  31. doi:10.1071/CH9891201
    .
  32. PMID 8021654
    .
  33. PMID 9677285
    .
  34. PMID 16378379
    .
  35. ISBN 978-1-4614-1541-1
    , retrieved 2021-11-16
  36. PMID 20036304
    .
  37. PMID 10421760
    .
  38. PMID 8270488
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Β-Carboline&oldid=1194115471"