Tyrosinase inhibitors: a patent review (2011-2015)

ABSTRACT

Introduction: Tyrosinase is responsible for melanin production. The overproduction of melanin causes many skin disorders. The inhibition of tyrosinase activity would appear to be the most rational and explicit way of overcoming these issues.

Areas covered: Thirty eight patents on synthetic tyrosinase inhibitors issued since 2011 were reviewed. Inhibitors were categorized by chemical structure and assigned to eight classes. Information on potent inhibitors in each class is provided.

Expert opinion: Many tyrosinase inhibitors of natural or synthetic origin have been identified, but very few are qualified for clinical use. Thus medicinal scientists have to work more on the identification of potent and safe tyrosinase inhibitors. Various chemical scaffolds have been explored. Among them, the scaffolds such as resorcinol, biaryl, imidazolethione, β-phenyl-α,β-unsaturated carbonyl, and some double strand oligonucleotides have shown high tyrosinase inhibition, low toxicities, and great potencies. Detail structure activity relationship studies of these potential scaffolds could provide directions for a new and potent tyrosinase inhbitors. Furthermore new trends, such as the use of synergistic phenomena, salt formation, drug repositioning and designing of multi-targeted tyrosinase inhibitors could expand search areas for much improved tyrosinase inhibitors.

KEYWORDS:

• Tyrosinase
• melanin
• melanogenesis
• hyperpigmentation
• synthetic inhibitors

Article highlights

• Resorcinol, biaryl, and imidazolethione are the important scaffolds for the inhibition of tyrosinase activity.

• β-Phenyl-α,β-unsaturated carbonyl and double-strand oligonucleotide inhibited tyrosinase activity and the expressions of tyrosine-related protein (TRP)-1, TRP-2, and microphthalmia-associated transcription factor.

• Drug repositioning concept can be used as a useful tool for the discovery of novel tyrosinase inhibitors.

• Synergistic approach towards tyrosinase inhibition through combination therapy can be helpful to treat hyperpigmentation.

• Salt formation of tyrosinase inhibitors can also enhance the potency of tyrosinase inhibitors through increased water solubility.

• To design and develop multitargeted tyrosinase inhibitors could provide a new trend towards the therapy of hyperpigmentation in the future.

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Declaration of Interest

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Korean Ministry of Education, Science and Technology (NRF-2013R1A1A2009949) and by a National Research Foundation of Korea grant funded by the Korean government (2009-008358). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.