Chemistry:Azelaic acid

From HandWiki
Short description: Organic chemical compound
"Finevin" redirects here. Finevin may also refer to a former settlement in Sutherland, Scotland.

Azelaic acid
Skeletal formula of azelaic acid
Ball-and-stick model of the azelaic acid molecule
Names
Preferred IUPAC name
Nonanedioic acid
Other names
Azelate
Identifiers
3D model (JSmol)
1101094
ChEBI
ChEMBL
ChemSpider
DrugBank
EC Number
  • 204-669-1
261342
KEGG
UNII
Properties
C9H16O4
Molar mass 188.223 g·mol−1
Appearance white solid
Density 1.443 g/mL
Melting point 109 to 111 °C (228 to 232 °F; 382 to 384 K)[1]
Boiling point 286 °C (547 °F; 559 K) at 100 mmHg[1]
2.14 g/L[2]
Acidity (pKa) 4.550, 5.498[2]
Pharmacology
1=ATC code }} D10AX03 (WHO)
Topical
Pharmacokinetics:
Very low
12 h
Legal status
  • AU: S5 (Caution) / Schedule 4,Schedule 2 Appendix E, clause 3 Appendix F, clause 4[3]
  • US: ℞-only [4]
Hazards
GHS pictograms GHS07: Harmful
GHS Signal word Warning
H315, H319
P264, P280, P302+352, P305+351+338, P321, P332+313, P337+313, P362
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 ?)
Infobox references
Tracking categories (test):
Azelaic acid
Clinical data
MedlinePlusa603020
License data

Azelaic acid (AzA), or nonanedioic acid, is an organic compound with the formula HOOC(CH2)7COOH.[5] 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.[6] In medicine, topical formulations of AzA are used in the treatment of acne vulgaris, where they exert antimicrobial and keratolytic effects that reduce clogged hair follicles and inflammation.[7] In plants, AzA functions as a mobile signaling molecule that primes systemic acquired resistance against pathogens by inducing the accumulation of salicylic acid.[8] AzA also inhibits tyrosinase.[9]

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.[10]

Biological function

Plants biology

In plants, azelaic acid (AzA) functions as an endogenous signaling molecule that plays a central role in systemic defense responses after infection. It acts as a "distress flare," produced primarily in response to biotic stress such as pathogen attack, and is transported from infected tissues to distant parts of the plant.[11] There, it primes systemic acquired resistance (SAR) against a broad spectrum of pathogens by inducing the accumulation of salicylic acid, a key component of the plant's immune response.[12] Mechanistically, AzA works in concert with other mobile signals, including glycerol-3-phosphate and specific lipid transfer proteins, to orchestrate a systemic defense network that enhances disease resistance and enables rapid defensive responses to subsequent infections.[13]

Human biology

Azelaic acid treats acne through a multifaceted mechanism that includes antibacterial, anti-keratinizing, and anti-inflammatory activities, as well as direct effects on skin microflora. It exerts bacteriostatic action against Propionibacterium acnes and Staphylococcus epidermidis by disrupting microbial cellular metabolism and membrane pH balance, resulting in reduced bacterial proliferation without promoting resistance. In keratinocytes, azelaic acid inhibits DNA, RNA, and protein synthesis, thus normalizing follicular keratinization, which helps prevent the formation of comedones—clogged hair follicles that can develop into acne lesions and are considered a hallmark of the disease. Additionally, its anti-inflammatory properties decrease the production of reactive oxygen species and pro-inflammatory cytokines, collectively reducing both visible inflammation and the severity of acne lesions.[7][14]

Applications

Azelaic acid cream labeled in Russian

Esters of this dicarboxylic acid find applications in lubrication and plasticizers. In lubricant industries, it is used as a thickening agent in lithium complex grease. With hexamethylenediamine, azelaic acid forms Nylon-6,9, which finds specialized uses as a plastic.[6]

Medical

In 2023, it was the 309th most commonly prescribed medication in the United States, with more than 200,000 prescriptions.[15]

Azelaic acid is used to treat mild to moderate acne, both comedonal acne and inflammatory acne.[16][17] 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[clarification needed] of acne bacteria.[18] Azelaic acid is also used as a topical gel treatment for rosacea, due to its ability to reduce inflammation.[17] 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.[19]

Acne treatment

Azelaic acid is effective for mild to moderate acne when applied topically at a 15%-20% concentration.[20][21][22][23] In patients with moderate acne, twice daily application over 3 months of 20% AzA significantly reduced the number of comedones, papules, and pustules;[24][25] 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.[26][27] 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.[28] 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.[26]

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.[29] As a tyrosinase inhibitor,[9] azelaic acid reduces synthesis of melanin.[30] 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.[31] In vitro research during mid-1980s evaluating azelaic acid's depigmenting (whitening) capability concluded it is effective (cytotoxic to melanocytes) at only high concentrations.[32]

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.[33][25]

Brand names

Brand names for azelaic acid include Dermaz 99,[34] 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)[35]

References

  1. ↑ 1.0 1.1 Sigma-Aldrich catalog
  2. ↑ 2.0 2.1 "Solubility and Activity Coefficients of Acidic and Basic Nonelectrolytes in Aqueous Salt Solutions. 2. Solubility and Activity Coefficients of Suberic, Azelaic, and Sebacic Acids in NaCl(aq), (CH3)4NCl(aq), and (C2H5)4NI(aq) at Different Ionic Strengths and at t = 25 °C". J. Chem. Eng. Data 51 (5): 1660–1667. 2006. doi:10.1021/je060132t. 
  3. ↑ "Therapeutic Goods (Poisons Standard— June 2025) Instrument 2025" (pdf). May 2025. https://www.legislation.gov.au/F2025L00599/asmade/2025-05-28/text/original/pdf. 
  4. ↑ "Finacea- azelaic acid gel; Finacea- azelaic acid kit". 12 April 2011. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=63773349-0295-4d56-a72e-0d7cade88ddb. 
  5. ↑ "The use of topical azelaic acid for common skin disorders other than inflammatory rosacea". Cutis 77 (2 Suppl): 22–24. February 2006. PMID 16566285. 
  6. ↑ 6.0 6.1 "Dicarboxylic Acids, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. 2006. doi:10.1002/14356007.a08_523. ISBN 978-3-527-30673-2. 
  7. ↑ 7.0 7.1 "Azelaic Acid: Mechanisms of Action and Clinical Applications". Clinical, Cosmetic and Investigational Dermatology 17: 2359–2371. 2024. doi:10.2147/CCID.S485237. PMID 39464747. 
  8. ↑ "Priming in systemic plant immunity". Science 324 (5923): 89–91. April 2009. doi:10.1126/science.1170025. PMID 19342588. Bibcode: 2009Sci...324...89W. 
  9. ↑ 9.0 9.1 "Skin whitening agents: medicinal chemistry perspective of tyrosinase inhibitors". Journal of Enzyme Inhibition and Medicinal Chemistry 32 (1): 403–425. December 2017. doi:10.1080/14756366.2016.1256882. PMID 28097901. 
  10. ↑ Integrative medicine (Fourth ed.). Philadelphia, PA: Elsevier Inc.. 2018. ISBN 978-0-323-35868-2. OCLC 982188831. 
  11. ↑ "Vegetative Warfare". Chemical & Engineering News 89 (5): 53–55. 31 January 2011. doi:10.1021/cen-v089n005.p053. http://cen.acs.org/articles/89/i5/Vegetative-Warfare.html. 
  12. ↑ "Priming in systemic plant immunity". Science 324 (5923): 89–91. April 2009. doi:10.1126/science.1170025. PMID 19342588. Bibcode: 2009Sci...324...89W. 
  13. ↑ "Lipid peroxidation and stress-induced signalling molecules in systemic resistance mediated by azelaic acid/AZELAIC ACID INDUCED1: signal initiation and propagation". Physiology and Molecular Biology of Plants 30 (2): 305–316. February 2024. doi:10.1007/s12298-024-01420-1. PMID 38623172. Bibcode: 2024PMBP...30..305P. 
  14. ↑ "Azelaic Acid: Evidence-based Update on Mechanism of Action and Clinical Application". Journal of Drugs in Dermatology 14 (9): 964–968. September 2015. PMID 26355614. 
  15. ↑ "Azelate Drug Usage Statistics, United States, 2013 - 2023". https://clincalc.com/DrugStats/Drugs/Azelate. 
  16. ↑ "Azelaic Acid for Acne". http://www.webmd.com/skin-problems-and-treatments/acne/azelaic-acid-for-acne-vulgaris. 
  17. ↑ 17.0 17.1 "Azelaic acid topical". https://www.drugs.com/mtm/azelaic-acid-topical.html. 
  18. ↑ "Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials". Archives of Dermatology 142 (8): 1047–1052. August 2006. doi:10.1001/archderm.142.8.1047. PMID 16924055. 
  19. ↑ "New effective azelaic acid liposomal gel formulation of enhanced pharmaceutical bioavailability". Biomedicine & Pharmacotherapy 83: 771–775. October 2016. doi:10.1016/j.biopha.2016.07.014. PMID 27484346. 
  20. ↑ "Azelaic acid: Properties and mode of action". Skin Pharmacology and Physiology 27 (Supplement 1): 9–17. November 2013. doi:10.1159/000354888. PMID 24280644. 
  21. ↑ "Treatment of acne vulgaris in pregnant patients". Dermatologic Therapy 26 (4): 302–311. July 2013. doi:10.1111/dth.12077. PMID 23914887. 
  22. ↑ "[Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies]". Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology 2 (10): 841–847. October 2004. doi:10.1046/j.1439-0353.2004.04731.x. PMID 16281587. 
  23. ↑ "Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris". Journal of Drugs in Dermatology 7 (1): 13–16. January 2008. PMID 18246693. 
  24. ↑ "Azelaic Acid And Its Benefits" (in en). https://chemistatplay.com/blogs/news/azelaic-acid-and-its-benefits. 
  25. ↑ 25.0 25.1 "Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders". Drugs 41 (5): 780–798. May 1991. doi:10.2165/00003495-199141050-00007. PMID 1712709. 
  26. ↑ 26.0 26.1 "Alternative therapies for common dermatologic disorders, part 2". Primary Care 37 (2): 285–296. June 2010. doi:10.1016/j.pop.2010.02.005. PMID 20493337. 
  27. ↑ "Retinoids and azelaic acid to treat acne and hyperpigmentation in skin of color". Journal of Drugs in Dermatology 12 (4): 434–437. April 2013. PMID 23652891. 
  28. ↑ "Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review". Journal of Evidence-Based Medicine 13 (4): 275–283. November 2020. doi:10.1111/jebm.12411. PMID 33034949. 
  29. ↑ "Skin lightening preparations and the hydroquinone controversy". Dermatologic Therapy 20 (5): 308–313. Sep–Oct 2007. doi:10.1111/j.1529-8019.2007.00144.x. PMID 18045355. 
  30. ↑ Aesthetics and Cosmetic Surgery for Darker Skin Types. Lippincott Williams & Wilkins. 1 July 2007. pp. 74 ff. ISBN 978-0-7817-8403-0. https://books.google.com/books?id=ALt93yGZccQC&pg=PA74. Retrieved 9 August 2011. 
  31. ↑ "Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid". The British Journal of Dermatology 119 (5): 627–632. November 1988. doi:10.1111/j.1365-2133.1988.tb03474.x. PMID 3207614. 
  32. ↑ "An evaluation of the effectiveness of azelaic acid as a depigmenting and chemotherapeutic agent". The Journal of Investigative Dermatology 85 (3): 222–228. September 1985. doi:10.1111/1523-1747.ep12276684. PMID 4031538. 
  33. ↑ "Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies". Cutis 57 (1 Suppl): 36–45. January 1996. PMID 8654129. 
  34. ↑ https://pharmaceutical.basf.com/en/APIs-Raw-Materials/Dermaz.html
  35. ↑ "Azelaic Acid brands in Pakistan". http://www.druginfosys.com/availablebrands.aspx?query=20%2520%25w/w&form=Cream&drugCode=807&drugName=Azelaic%2520Acid&type=1&Ing==1. 




Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Azelaic_acid&oldid=4038254"