Azelaic acid therapy in disorders of pigmentation

Breathnach, Aodán C.; Nazzaro‐Porro, M.; Passi, S.; Zina, G

doi:10.1016/0738-081x(89)90061-8

Cited by 54 publications

(32 citation statements)

References 19 publications

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“…13,14 Therefore, tyrosinase is a crucial topic in the fields of medicine, agriculture, and cosmetics, and considerable attention has been paid to developing and screening for tyrosinase inhibitors. 15 Some tyrosinase inhibitors, such as hydroquinone, 16,17 arbutin, 18 kojic acid, 19,20 azelaic acid, 21,22 and electron-rich phenols, 23 have been used in cosmetics. However, only a few such inhibitors are sufficiently potent for practical use and are in compliance with safety regulations.…”

Section: ■ Introductionmentioning

confidence: 99%

Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation

Tseng

Tsai

Chen

et al. 2015

J. Agric. Food Chem.

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Tyrosinase is an essential copper-containing enzyme required for melanin synthesis. The overproduction and abnormal accumulation of melanin cause hyperpigmentation and neurodegenerative diseases. Thus, tyrosinase is promising for use in medicine and cosmetics. Our previous study identified a natural product, A5, resembling the structure of the dipeptide WY and apparently inhibiting tyrosinase. Here, we comprehensively estimated the inhibitory capability of 20 × 20 dipeptides against mushroom tyrosinase. We found that cysteine-containing dipeptides, directly blocking the active site of tyrosinase, are highly potent in inhibition; in particular, N-terminal cysteine-containing dipeptides markedly outperform the C-terminal-containing ones. The cysteine-containing dipeptides, CE, CS, CY, and CW, show comparative bioactivities, and tyrosine-containing dipeptides are substrate-like inhibitors. The dipeptide PD attenuates 16.5% melanin content without any significant cytotoxicity. This study reveals the functional role of cysteine residue positional preference and the selectivity of specific amino acids in cysteine-containing dipeptides against tyrosinase, aiding in developing skin-whitening products.

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Section: ■ Introductionmentioning

confidence: 99%

Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation

Tseng

Tsai

Chen

et al. 2015

J. Agric. Food Chem.

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“…Tyrosinase inhibitors, such as hydroquinone (Arndt and Fitzpatrick, 1965;Fitzpatrick et al, 1966), arbutin (Germanas et al, 2007), kojic acid (Mishima et al, 1988;Elsner and Maibach, 2000;Ahn et al, 2011), azelaic acid (Breathnach et al, 1989;Rigoni et al, 1989), and electron-rich phenols (Jimbow, 1991), have been tested in cosmetics and pharmaceuticals for their ability to prevent the overproduction of melanin. Although these compounds can effectively inhibit tyrosinase activity, their use is strictly limited because they cause skin allergies, inflammation, and other adverse side effects.…”

Section: Introductionmentioning

confidence: 99%

Phage Display–Mediated Discovery of Novel Tyrosinase-Targeting Tetrapeptide Inhibitors Reveals the Significance of N-Terminal Preference of Cysteine Residues and Their Functional Sulfur Atom

et al. 2014

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Tyrosinase, a key copper-containing enzyme involved in melanin biosynthesis, is closely associated with hyperpigmentation disorders, cancer, and neurodegenerative diseases, and as such, it is an essential target in medicine and cosmetics. Known tyrosinase inhibitors possess adverse side effects, and there are no safety regulations; therefore, it is necessary to develop new inhibitors with fewer side effects and less toxicity. Peptides are exquisitely specific to their in vivo targets, with high potencies and relatively few off-target side effects. Thus, we systematically and comprehensively investigated the tyrosinase-inhibitory abilities of N-and C-terminal cysteine/tyrosine-containing tetrapeptides by constructing a phage-display random tetrapeptide library and conducting computational molecular docking studies on novel tyrosinase tetrapeptide inhibitors. We found that N-terminal cysteine-containing tetrapeptides exhibited the most potent tyrosinase-inhibitory abilities. The positional preference of cysteine residues at the N terminus in the tetrapeptides significantly contributed to their tyrosinase-inhibitory function. The sulfur atom in cysteine moieties of N-and C-terminal cysteine-containing tetrapeptides coordinated with copper ions, which then tightly blocked substrate-binding sites. N-and C-terminal tyrosinecontaining tetrapeptides functioned as competitive inhibitors against mushroom tyrosinase by using the phenol ring of tyrosine to stack with the imidazole ring of His263, thus competing for the substrate-binding site. The N-terminal cysteine-containing tetrapeptide CRVI exhibited the strongest tyrosinase-inhibitory potency (with an IC 50 of 2.7 6 0.5 mM), which was superior to those of the known tyrosinase inhibitors (arbutin and kojic acid) and outperformed kojic acid-tripeptides, mimosine-FFY, and shortsequence oligopeptides at inhibiting mushroom tyrosinase.

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“…Inducing the degradation of melanin and melanosomes is another way to fight hyperpigmentation [60]. Due to its inhibitory effect on tyrosinase, AzA has been used to treat melasma [61,62,63,64], lentigo maligna and postinflammatory hyperpigmentation [61,62,65]. In vitro studies show that AzA interferes with DNA synthesis and mitochondrial enzymes in abnormal melanocytes, but does not affect normal melanocytes [66].…”

Section: Influence Of Aza On Melanogenesismentioning

confidence: 99%

Azelaic Acid: Properties and Mode of Action

Sieber

Hegel²

2013

Skin Pharmacol Physiol

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Acne is a common skin disorder that can be problematic for adults as well as for adolescents. It has several key pathophysiological features such as follicular hyperkeratosis, elevated Propionibacterium acnes proliferation, and reactive inflammation, all of which should be targeted for an optimal outcome. Azelaic acid (AzA) has profound anti-inflammatory, antioxidative effects, and is bactericidal against a range of Gram-negative and Gram-positive microorganisms as well, including antibiotic-resistant bacterial strains. In addition, AzA's antikeratinizing effects are inhibitory toward comedones. AzA is effective overall in targeting multiple causes of acne and has been proven to be well tolerated in numerous clinical trials.

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Azelaic acid therapy in disorders of pigmentation

Cited by 54 publications

References 19 publications

Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation

Discovery of Potent Cysteine-Containing Dipeptide Inhibitors against Tyrosinase: A Comprehensive Investigation of 20 × 20 Dipeptides in Inhibiting Dopachrome Formation

Phage Display–Mediated Discovery of Novel Tyrosinase-Targeting Tetrapeptide Inhibitors Reveals the Significance of N-Terminal Preference of Cysteine Residues and Their Functional Sulfur Atom

Azelaic Acid: Properties and Mode of Action

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