Enoxolone

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Enoxolone
Glycyrrhetinic acid structure.svg
Systematic (IUPAC) name
(2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxylic acid
Clinical data
Trade names Arthrodont, PruClair
AHFS/Drugs.com International Drug Names
Legal status
Routes of
administration		 Oral, topical
Identifiers
CAS Number 471-53-4
ATC code D03AX10 (WHO)
PubChem CID: 10114
ChemSpider 9710
ChEBI CHEBI:30853
ChEMBL CHEMBL230006
Chemical data
Formula C30H46O4
Molecular mass 470.6838
  • O=C(O)[C@]5(C)C[C@H]4/C3=C/C(=O)[C@H]1[C@](CC[C@@H]2[C@]1(C)CC[C@H](O)C2(C)C)(C)[C@]3(C)CC[C@@]4(C)CC5
  • InChI=1S/C30H46O4/c1-25(2)21-8-11-30(7)23(28(21,5)10-9-22(25)32)20(31)16-18-19-17-27(4,24(33)34)13-12-26(19,3)14-15-29(18,30)6/h16,19,21-23,32H,8-15,17H2,1-7H3,(H,33,34)/t19-,21-,22-,23+,26+,27-,28-,29+,30+/m0/s1
  • Key:MPDGHEJMBKOTSU-YKLVYJNSSA-N

Enoxolone (INN, BAN; also known as glycyrrhetinic acid or glycyrrhetic acid) is a pentacyclic triterpenoid derivative of the beta-amyrin type obtained from the hydrolysis of glycyrrhizic acid, which was obtained from the herb liquorice. It is used in flavoring and it masks the bitter taste of drugs like aloe and quinine. It is effective in the treatment of peptic ulcer and also has expectorant (antitussive) properties.[1] It has some additional pharmacological properties including antiviral, antifungal, antiprotozoal, and antibacterial activities.[2][3][4][5]

Mechanism of action

Glycyrrhetinic acid inhibits the enzymes (15-hydroxyprostaglandin dehydrogenase and delta-13-prostaglandin) that metabolize the prostaglandins PGE-2 and PGF-2α to their respective 15-keto-13,14-dihydro metabolites which are inactive.[citation needed] This causes an increased level of prostaglandins in the digestive system.[citation needed] Prostaglandins inhibit gastric secretion but stimulate pancreatic secretion and mucous secretion in the intestines and markedly increase intestinal motility.[citation needed] They also cause cell proliferation in the stomach.[citation needed] The effect on gastric acid secretion, promotion of mucous secretion and cell proliferation shows why licorice has potential in treating peptic ulcer.[citation needed]

PGF-2α stimulates activity of the uterus during pregnancy and can cause abortion, therefore, licorice should not be taken during pregnancy.[citation needed]

The structure of glycyrrhetinic acid is similar to that of cortisone. Both molecules are flat and similar at position 3 and 11. This might be the basis for licorice's anti-inflammatory action.[citation needed]

3-β-D-(Monoglucuronyl)-18-β-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid, inhibits the conversion of 'active' cortisol to 'inactive' cortisone in the kidneys.[6] This occurs via inhibition of the enzyme by inhibiting the enzyme 11-β-hydroxysteroid dehydrogenase.[citation needed] As a result, cortisol levels are high within the collecting duct of the kidney. Cortisol has intrinsic mineralocorticoid properties (that is, it acts like aldosterone and increases sodium reabsorption) that work on ENaC channels in the collecting duct.[citation needed]Hypertension develops due to this mechanism of sodium retention. People often have high blood pressure with a low renin and low aldosterone blood level.[citation needed] The increased amounts of cortisol binds to the unprotected, unspecific mineralocorticoid receptors and induce sodium and fluid retention, hypokalaemia, high blood pressure and inhibition of the renin-angiotensin-aldosterone system. Therefore, licorice should not be given to patients with a known history of hypertension in doses sufficient to inhibit 11-β-hydroxysteroid dehydrogenase.[citation needed]

Derivatives

Glycyrrhetinic acid derivatives, where R is a variable functional group

In glycyrrhetinic acid, the functional group (R) is a hydroxyl group. Research in 2005 demonstrated that with a proper functional group a very effective glycyrrhetinic artificial sweetener can be obtained.[7] When R is an anionic NHCO(CH2)CO2K side chain, the sweetening effect is found to 1200 times that of sugar (human sensory panel data). A shorter or longer spacer reduces the sweetening effect. One explanation is that the taste bud cell receptor has 1.3 nanometers (13 angstroms) available for docking with the sweetener molecule. In addition the sweetener molecule requires three proton donor positions of which two reside at the extremities to be able to interact efficiently with the receptor cavity.

A synthetic analog, carbenoxolone, was developed in Britain.[citation needed] Both glycyrrhetinic acid and carbenoxolone have a modulatory effect on neural signaling through gap junction channels.

Acetoxolone, the acetyl derivative of glycyrrhetinic acid, is a drug used in the treatment of peptic ulcer and gastroesophageal reflux disease.

References

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  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.

Further reading

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