However, by far the most potent inhibitor of human tyrosinase is
Swertiajaponin is the strongest tyrosinase inhibitor of fifty flavonoids. Of various natural compounds, flavonoids, a group of naturally occurring antioxidants and metal chelators, have been known to suppress tyrosinase activity because of their ability to form copper-flavonoid complexes [8, 9].
Tyrosinase inhibitors include flavone, morusone, biflavone 3-O-β-D-glucosyl 4,5,5,7,7-pentahydroxy 3,3-dimethoxy 3,4-O-biflavone, flavone glucoside vitexin, and a C-glycosyl flavone isovitexin [34,35,36].
T1 compound and bis-4-hydroxybenzyl sulfide is a competitive-type inhibitor to tyrosinase that is comparable to kojic acid. Molecular modeling analysis has shown that the sulfur atom's T1 coordination with copper ions at the enzyme active site represents a key inhibitory activity [86].
Many tyrosinase inhibitors such as hydroquinone (HQ)31–34, arbutin, kojic acid35–37, azelaic acid38,39, L-ascorbic acid40–42, ellagic acid43–45, tranexamic acid46–48 have been used as skin-whitening agents, with certain drawbacks (Figure 3).
Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation. It is found inside melanosomes which are synthesized in the skin melanocytes.
An example of a competitive inhibitor is the antineoplastic drug methotrexate. Methotrexate has a structure similar to that of the vitamin folic acid (Fig. 4-5). It acts by inhibiting the enzyme dihydrofolate reductase, preventing the regeneration of dihydrofolate from tetrahydrofolate.
Alpha-arbutin: A gentle on the skin derivative of hydroquinone that blocks tyrosinase activity. Skincare professionals use it extensively since it is effective and lowers irritation risk. Kojic Acid: Naturally produced by fungus, kojic acid contains antioxidant and tyrosinase-inhibiting qualities.
Finally, vitamin C is a well-known antioxidant that inhibits tyrosinase by interacting with copper ions at tyrosinase active sites, thus decreasing melanogenesis [10].
Tretinoin is another topical pharmacological agent that acts by inhibiting the activity of tyrosinase.
The most active compound, 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), was found to be a significant tyrosinase activator. The maximal activation was 126% at a concentration of 75.0 microg/mL. The three anthraquinones slightly activated tyrosinase with effects in the range 7-31%.
Conclusions. We conclude that azelaic acid may be better than hydroquinone in reducing melasma severity as measured by the MASI. However, no significant difference between both treatments regarding the side effects.
Tyrosine also helps produce melanin, the pigment responsible for hair and skin color. It helps in the function of organs responsible for making and regulating hormones, including the adrenal, thyroid, and pituitary glands.
Monobenzyl ether of hydroquinone (MBEH) is a hydroquinone derivate, also known as monobenzone or by its chemical name, p-(benzyloxy) phenol. At present, it is the most potent depigmenting agent and the mainstay of depigmentation therapy.
Competitive inhibition can be reversible or irreversible. If it is reversible inhibition, then effects of the inhibitor can be overcome by increasing substrate concentration.
Ibuprofen (IBP) has classically fallen into the time-independent class of COX inhibitors as it binds rapidly and reversibly to COX and acts as a competitive inhibitor of arachidonic acid (AA) oxygenation (Gierse et al., 1999, Prusakiewicz et al., 2009).
What Are Irreversible Inhibitors? Irreversible inhibitors are inhibitors that bind to enzymes and inactivate them, making the substrate concentration irrelevant (i.e., adding more substrate does not reverse the enzyme inhibition). They are non-competitive in nature.
They have found hydroquinone and arbutin and kojic acid (IC50 > 500 µmol/L) weekly inhibits human tyrosinase. In contrast, a resorcinyl-thiazole derivative, thiamidol, is a most potent inhibitor of human tyrosinase (IC50 of 1.1 µmol/L) but inhibits mushroom tyrosinase weakly (IC50 = 108 µmol/L)130.
The FAH gene provides instructions for making an enzyme called fumarylacetoacetate hydrolase, which performs the last step of tyrosine breakdown. The enzyme produced from the TAT gene, called tyrosine aminotransferase enzyme, is involved in the first step in the process.
Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinases. We analyzed the effects of genistein on in vitro growth, cell-cycle progression and chromatin structure of Jurkat cells, a T-cell leukemia line with a constitutively increased tyrosine phosphorylation pattern.
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Targeted therapy drugs commonly used for CML
The TKIs used to treat CML are given as pills. Imatinib (Gleevec) was the first TKI developed to treat CML. Almost everyone diagnosed with CML will be given imatinib as the first treatment.