azelaic acid
{{Short description|Organic chemical compound}}
{{Redirect-synonym|Finevin|a former settlement in Sutherland, Scotland}}
{{Use dmy dates|date=December 2024}}
{{chembox
| Watchedfields = changed
| verifiedrevid = 458792195
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageFile = Azelaic acid.png
| ImageSize = 255px
| ImageAlt = Skeletal formula of azelaic acid
| ImageFile1 = Azelaic acid 3D ball.png
| ImageSize1 = 255px
| ImageAlt1 = Ball-and-stick model of the azelaic acid molecule
| PIN = Nonanedioic acid
| OtherNames = Azelate
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 7484
| EC_number = 204-669-1
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1238
| Beilstein = 1101094
| Gmelin = 261342
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00548
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = F2VW3D43YT
| InChIKey = BDJRBEYXGGNYIS-UHFFFAOYAK
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C9H16O4/c10-8(11)6-4-2-1-3-5-7-9(12)13/h1-7H2,(H,10,11)(H,12,13)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = BDJRBEYXGGNYIS-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 123-99-9
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2179
| PubChem = 2266
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03034
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 48131
| SMILES = O=C(O)CCCCCCCC(=O)O
| InChI = 1/C9H16O4/c10-8(11)6-4-2-1-3-5-7-9(12)13/h1-7H2,(H,10,11)(H,12,13)
}}
|Section2={{Chembox Properties
| C=9 | H=16 | O=4
| MolarMass =
| Appearance = white solid
| Density = 1.443 g/mL
| MeltingPtC = 109 to 111
| BoilingPtC = 286
| BoilingPt_notes = at 100 mmHg
}}
|Section6={{Chembox Pharmacology
| Pharmacology_ref =
| ATCCode_prefix = D10
| ATCCode_suffix = AX03
| ATC_Supplemental =
| ATCvet =
| Licence_EU =
| INN =
| INN_EMA =
| Licence_US =
| Legal_status =
| Legal_AU = S2
| Legal_AU_comment =
| Legal_CA =
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| Legal_NZ =
| Legal_NZ_comment =
| Legal_UK =
| Legal_UK_comment =
| Legal_US = Rx-only
| Legal_US_comment =
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| Pregnancy_category =
| Pregnancy_AU =
| Pregnancy_AU_comment =
| Dependence_liability =
| AdminRoutes = Topical
| Bioavail = Very low
| ProteinBound =
| Metabolism =
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| OnsetOfAction =
| HalfLife = 12 h
| DurationOfAction =
| Excretion =
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|Section7={{Chembox Hazards
| GHSPictograms = {{GHS07}}
| GHSSignalWord = Warning
| HPhrases = {{H-phrases|315|319}}
| PPhrases = {{P-phrases|264|280|302+352|305+351+338|321|332+313|337+313|362}}
}}
}}
Azelaic acid (AzA), or nonanedioic acid, is an organic compound with the formula HOOC(CH2)7COOH.{{Cite journal|last=Del Rosso|first=James Q.|date=1 February 2006|title=The use of topical azelaic acid for common skin disorders other than inflammatory rosacea|url=https://pubmed.ncbi.nlm.nih.gov/16566285/|journal=Cutis|volume=77|issue=2 Suppl|pages=22–24|issn=0011-4162|pmid=16566285}} This saturated dicarboxylic acid exists as a white powder. It is found in wheat, rye, and barley. It is a precursor to diverse industrial products including polymers and plasticizers, as well as being a component of several hair and skin conditioners. AzA inhibits tyrosinase.
Production
Azelaic acid is industrially produced by the ozonolysis of oleic acid. The side product is nonanoic acid. It is produced naturally by Malassezia furfur (also known as Pityrosporum ovale), a yeast that lives on normal skin. The bacterial degradation of nonanoic acid gives azelaic acid.{{Cite book|url=https://www.worldcat.org/oclc/982188831|title=Integrative medicine|date=2018|others=David Rakel|isbn=978-0-323-35868-2|edition=Fourth|location=Philadelphia, PA|chapter=|oclc=982188831}}
Biological function
=Plants biology=
In plants, azelaic acid serves as a "distress flare" involved in defense responses after infection.{{cite journal | author = Sarah Everts | title = Vegetative Warfare | journal = Chemical & Engineering News | date=31 January 2011 | volume = 89 | issue = 5 | pages = 53–55 | doi = 10.1021/cen-v089n005.p053 | url=http://cen.acs.org/articles/89/i5/Vegetative-Warfare.html |url-access=subscription }} It serves as a signal that induces the accumulation of salicylic acid, an important component of a plant's defensive response.{{Cite journal | last1 = Jung | first1 = H. W. | last2 = Tschaplinski | first2 = T. J. | last3 = Wang | first3 = L. | last4 = Glazebrook | first4 = J. | last5 = Greenberg | first5 = J. T. | title = Priming in Systemic Plant Immunity | journal = Science | volume = 324 | issue = 5923 | pages = 89–91 | year = 2009 | pmid = 19342588 | doi = 10.1126/science.1170025| bibcode = 2009Sci...324...89W | s2cid = 206518245 }}
=Human biology=
The mechanism of action in humans is thought to be through the inhibition of hyperactive protease activity that converts cathelicidin into the antimicrobial skin peptide LL-37.{{cite journal | pmc=3346901| year=2012| last1=Reinholz| first1=M.| title=Cathelicidin LL-37: An Antimicrobial Peptide with a Role in Inflammatory Skin Disease| journal=Annals of Dermatology| volume=24| issue=2| pages=126–135| last2=Ruzicka| first2=T.| last3=Schauber| first3=J.| doi=10.5021/ad.2012.24.2.126| pmid=22577261}}
Applications
=Medical=
In 2022, it was the 298th most commonly prescribed medication in the United States, with more than 300,000 prescriptions.{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}{{cite web | title = Azelate Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Azelate | access-date = 30 August 2024 }}
Azelaic acid is used to treat mild to moderate acne, both comedonal acne and inflammatory acne.{{cite web|url=http://www.webmd.com/skin-problems-and-treatments/acne/azelaic-acid-for-acne-vulgaris |title=Azelaic Acid for Acne|website=WebMD}}{{cite web|url=https://www.drugs.com/mtm/azelaic-acid-topical.html |title=Azelaic acid topical|website=Drugs.com}} It belongs to a class of chemicals called dicarboxylic acids. It works by killing acne bacteria that infect skin pores. It also decreases the production of keratin, which is a natural substance that promotes the growth{{clarify|reason=Not wrong, but feels very off describing the main component of skin like this…|date=December 2021}} of acne bacteria.{{cite journal | title = Azelaic acid in the treatment of papulopustular rosacea – A systematic review of randomized controlled trials | last1 = Liu | first1 = R. H. | last2 = Smith | first2 = M. K. | last3 = Basta | first3 = S. A. | last4 = Farmer | first4 = E. R. | journal = Archives of Dermatology | volume = 142 | issue = 8 | pages = 1047–1052 | year = 2006 | doi =10.1001/archderm.142.8.1047 | pmid = 16924055 }} Azelaic acid is also used as a topical gel treatment for rosacea, due to its ability to reduce inflammation. It clears the bumps and swelling caused by rosacea.
In topical pharmaceutical preparations and scientific research AzA is typically used in concentrations between 15% and 20% but some research demonstrates that in certain vehicle formulations, the pharmaceutical effects of 10% Azelaic acid have the potential to be fully comparable to that of some 20% creams.{{Cite journal|date=1 October 2016|title=New effective azelaic acid liposomal gel formulation of enhanced pharmaceutical bioavailability|url=https://www.sciencedirect.com/science/article/abs/pii/S0753332216306278|journal=Biomedicine & Pharmacotherapy|language=en|volume=83|pages=771–775|doi=10.1016/j.biopha.2016.07.014|issn=0753-3322|last1=Burchacka|first1=E.|last2=Potaczek|first2=P.|last3=Paduszyński|first3=P.|last4=Karłowicz-Bodalska|first4=K.|last5=Han|first5=T.|last6=Han|first6=S.|pmid=27484346}}
==Acne treatment==
Azelaic acid is effective for mild to moderate acne when applied topically at a 15%-20% concentration.{{cite journal|vauthors=Sieber MA, Hegel JK|date=November 2013|title=Azelaic acid: Properties and mode of action|journal=Skin Pharmacology and Physiology|type=Review|volume=27 Suppl 1|issue=Supplement 1|pages=9–17|doi=10.1159/000354888|pmid=24280644|s2cid=8848543}}{{cite journal|vauthors=Pugashetti R, Shinkai K|date=July 2013|title=Treatment of acne vulgaris in pregnant patients|journal=Dermatologic Therapy|type=Review|volume=26|issue=4|pages=302–11|doi=10.1111/dth.12077|pmid=23914887|s2cid=5750718|doi-access=free}}{{Cite journal|last1=Gollnick|first1=H. P.|last2=Graupe|first2=K.|last3=Zaumseil|first3=R. P.|year=2004|title=15% Azelainsauregel in der Behandlung der Akne. Zwei doppelblinde klinische Vergleichsstudien|trans-title=Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies|url=http://europepmc.org/article/med/16281587|journal=Journal der Deutschen Dermatologischen Gesellschaft|volume=2|issue=10|pages=841–847|doi=10.1046/j.1439-0353.2004.04731.x|pmid=16281587|s2cid=58809558 |access-date=14 May 2021}}{{Cite journal|last=Thiboutot|first=Diane|date=January 2008|title=Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris|url=https://pubmed.ncbi.nlm.nih.gov/18246693/|journal=Journal of Drugs in Dermatology|volume=7|issue=1|pages=13–16|issn=1545-9616|pmid=18246693}} In patients with moderate acne, twice daily application over 3 months of 20% AzA significantly reduced the number of comedones, papules, and pustules;{{Cite web |title=Azelaic Acid And Its Benefits |url=https://chemistatplay.com/blogs/news/azelaic-acid-and-its-benefits |access-date=10 March 2022 |website=Chemist at Play |language=en}}{{Cite journal|last1=Fitton|first1=A.|last2=Goa|first2=K. L.|date=May 1991|title=Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders|url=https://pubmed.ncbi.nlm.nih.gov/1712709/|journal=Drugs|volume=41|issue=5|pages=780–798|doi=10.2165/00003495-199141050-00007|issn=0012-6667|pmid=1712709|s2cid=46960738}} at this strength, it’s considered to be as effective as benzoyl peroxide 5%, tretinoin 0.05%, erythromycin 2%, and oral tetracycline at 500 mg-1000 mg.{{cite journal|vauthors=Morelli V, Calmet E, Jhingade V|date=June 2010|title=Alternative therapies for common dermatologic disorders, part 2|journal=Primary Care|type=Review|volume=37|issue=2|pages=285–96|doi=10.1016/j.pop.2010.02.005|pmid=20493337}}{{Cite journal|last1=Woolery-Lloyd|first1=Heather C.|last2=Keri|first2=Jonette|last3=Doig|first3=Stefan|date=1 April 2013|title=Retinoids and azelaic acid to treat acne and hyperpigmentation in skin of color|url=https://pubmed.ncbi.nlm.nih.gov/23652891/|journal=Journal of Drugs in Dermatology|volume=12|issue=4|pages=434–437|issn=1545-9616|pmid=23652891}} In a comparative review of effects of topical AzA, Salicylic acid, Nicotinamide, Sulfur, Zinc, and alpha-hydroxy acid, AzA had more high-quality evidence of effectiveness than the rest.{{Cite journal|last1=Liu|first1=Haibo|last2=Yu|first2=Haiyan|last3=Xia|first3=Jun|last4=Liu|first4=Ling|last5=Liu|first5=Guanjian|last6=Sang|first6=Hong|last7=Peinemann|first7=Frank|date=1 November 2020|title=Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review|url=https://pubmed.ncbi.nlm.nih.gov/33034949/|journal=Journal of Evidence-Based Medicine|volume=13|issue=4|pages=275–283|doi=10.1111/jebm.12411|issn=1756-5391|pmid=33034949|s2cid=222236883}} Results can be expected after 4 weeks of twice-daily treatment. The effectiveness of long-term use is unclear, but it’s been recommended that AzA be used for at least 6 months continuously for maintenance.
=Whitening agent=
Azelaic acid is used for the treatment of skin pigmentation, including melasma and postinflammatory hyperpigmentation, particularly in those with darker skin types. It has been recommended as an alternative to hydroquinone.{{cite journal | last= Draelos |first=Z. | title = Skin lightening preparations and the hydroquinone controversy. | journal = Dermatologic Therapy | volume = 20 | issue = 5 | pages = 308–313 | date = Sep–Oct 2007 | pmid = 18045355 | doi=10.1111/j.1529-8019.2007.00144.x|s2cid=24913995 | doi-access = free }} As a tyrosinase inhibitor,{{Cite journal|last1=Pillaiyar|first1=Thanigaimalai|last2=Manickam|first2=Manoj|last3=Namasivayam|first3=Vigneshwaran|date=18 January 2017|title=Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors|journal=Journal of Enzyme Inhibition and Medicinal Chemistry|volume=32|issue=1|pages=403–425|doi=10.1080/14756366.2016.1256882|issn=1475-6366|pmc=6010116|pmid=28097901}} azelaic acid reduces synthesis of melanin.{{cite book|last=Grimes|first=Pearl E.|title=Aesthetics and Cosmetic Surgery for Darker Skin Types|url=https://books.google.com/books?id=ALt93yGZccQC&pg=PA74|access-date=9 August 2011|date=1 July 2007|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-8403-0|pages=74 ff}} According to one report in 1988, azelaic acid in combination with zinc sulfate in vitro was found to be a potent (90% inhibition) 5α-reductase inhibitor, similar to the hair loss drugs finasteride and dutasteride.{{cite journal |doi=10.1111/j.1365-2133.1988.tb03474.x |pmid=3207614 |title=Inhibition of 5α-reductase activity in human skin by zinc and azelaic acid |journal=British Journal of Dermatology |volume=119 |issue=5 |pages=627–32 |year=1988 |last1=Stamatiadis |first1=D |last2=Bulteau-Portois |first2=Marie-Claire |last3=Mowszowicz |first3=Irene |s2cid=28506969 }} In vitro research during mid-1980s evaluating azelaic acid's depigmenting (whitening) capability concluded it is effective (cytotoxic to melanocytes) at only high concentrations.{{Cite journal|last1=Pathak|first1=M. A.|last2=Ciganek|first2=E. R.|last3=Wick|first3=M.|last4=Sober|first4=A. J.|last5=Farinelli|first5=W. A.|last6=Fitzpatrick|first6=T. B.|date=September 1985|title=An evaluation of the effectiveness of azelaic acid as a depigmenting and chemotherapeutic agent|journal=The Journal of Investigative Dermatology|volume=85|issue=3|pages=222–228|doi=10.1111/1523-1747.ep12276684|issn=0022-202X|pmid=4031538|doi-access=free}}
A 1996 review claimed 20% AzA is as potent as 4% hydroquinone after a period of application of three months without the latter's adverse effects and even more effective if applied along with tretinoin for the same period of time.{{Cite journal|last=Breathnach|first=A. S.|date=1 January 1996|title=Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies|url=https://pubmed.ncbi.nlm.nih.gov/8654129/|journal=Cutis|volume=57|issue=1 Suppl|pages=36–45|issn=0011-4162|pmid=8654129}}
Brand names
Brand names for azelaic acid include Dermaz 99,https://pharmaceutical.basf.com/en/APIs-Raw-Materials/Dermaz.html{{full citation needed|date=September 2018}}{{Dead link|date=June 2020 |bot=InternetArchiveBot |fix-attempted=yes }} Crema Pella Perfetta (micronized azelaic acid, kojic dipalmitate, and liquorice extract), Azepur99, Azetec99, Azaclear (azelaic acid and niacinamide), AzClear Action, Azelex, White Action cream, Finacea, Finevin, Melazepam, Skinoren, Ezanic, Azelac, Azelan, Azaderm, (Acnegen, Eziderm, Acnicam, Azelexin in Pakistan){{Cite web|title=Azelaic Acid brands in Pakistan|url=http://www.druginfosys.com/availablebrands.aspx?query=20%2520%25w/w&form=Cream&drugCode=807&drugName=Azelaic%2520Acid&type=1&Ing==1|access-date=17 April 2021|website=www.druginfosys.com}}
References
{{reflist|30em}}
External links
- {{DermNet|treatments/azelaic-acid}}
- {{cite web|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a603020.html |title=Azelaic Acid Topical |website=MedlinePlus}}
{{Acne Agents}}
{{Androgenics}}
{{Navbox linear saturated dicarboxylic acids}}
Category:5α-Reductase inhibitors