Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances

Abstract

Tyrosinase is a copper-containing enzyme which is widely distributed in nature (e.g., bacteria, mammals, fungi) and involved in two consecutive steps of melanin biosynthesis. In humans, an excessive production of melanin can determine hyperpigmentation disorders as well as neurodegenerative processes in Parkinson’s disease. The development of molecules able to inhibit the high activity of the enzyme remain a current topic in medicinal chemistry, because the inhibitors reported so far present several side effects. Heterocycle-bearing molecules are largely diffuse in this sense. Due to their importance as biologically active compounds, we decided to report a comprehensive review of synthetic tyrosinase inhibitors possessing heterocyclic moieties reported within the last five years. For the reader’s convenience, we classified them as inhibitors of mushroom tyrosinase (Agaricus bisporus) and human tyrosinase.

Syntheses, reactivity, and biological applications of coumarins

“…Tyrosinase (Tyr) is a key enzyme in the biosynthesis of melanin pigments ( Mirabile et al, 2021 ). An excessive production of melanin can cause hyperpigmentation disorders such as melanoma ( Vittorio et al, 2023 ). Kim and co-workers described a new series of thiophenyl-pyrazolylthiazole-coumarin hybrids as tyrosinase inhibitors ( Nasab et al, 2023 ).…”

Bacterial Tyrosinase Inhibition, Hemolytic and Thrombolytic Screening, and In Silico Modeling of Rationally Designed Tosyl Piperazine-Engrafted Dithiocarbamate Derivatives

“…1.14.18.1) is a ubiquitous, naturally occurring, multi-copper-containing enzyme involved in the synthesis of various types of melanin pigments. This process is called melanogenesis and can be found in microorganisms (bacteria and fungi), mammals, and plants (fruits and vegetables) [2][3][4]. In the biosynthetic route of melanin synthesis, monophenol (L-tyrosine) can be converted into diphenol (L-DOPA) by utilizing tyrosinase as a catalyst (cresolase or monophenolase activity), and tyrosinase further catalyzes this intermediate product, L-DOPA, to convert it into dopaquinone (catecholase or diphenolase activity).…”

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

“…However, overproduction of melanin results in epidermal pigmentation, thereby causing skin hyperpigmentation disorders, including melasma, age spots, and freckles [ 20 , 21 , 22 ]. Inhibiting tyrosinase activity can reduce the formation of melanin; thereby, tyrosinase inhibitors can be utilized to prevent melanin-related diseases [ 23 , 24 ]. In addition, tyrosine inhibitors also can be utilized as effective food preservatives to delay food browning [ 25 , 26 , 27 ].…”

“…In addition, hybrids of pharmacophoric moieties have been an important part of the strategy to design new compound molecules with increased affinity and efficacy [ 24 , 48 ]. Therefore, as part of our ongoing efforts to find more potential tyrosinase inhibitors, the hybrids of the natural products cinnamic acid and eugenol were synthesized, followed by anti-tyrosinase activity screening, spectroscopic mechanism investigation, and a docking study.…”