Tyrosinase Inhibition and Antimelanogenic Effects of Resorcinol-Containing Compounds.

Tyrosinases (TYRs) are copper-containing metalloenzymes present in a large diversity of species. In human, hTYR is responsible for pivotal steps in melanogenesis, catalysing the oxidation of l-tyrosine to l-DOPA and further to dopaquinone. While numerous TYR inhibitors have been reported, polyphenolic compounds tend to dominate the literature.

Design and synthesis of 4-amino-2',4'-dihydroxyindanone derivatives as potent inhibitors of tyrosinase and melanin biosynthesis in human melanoma cells.

Melanogenesis inhibition constitutes a privileged therapeutic solution to treat skin hyperpigmentation, a major dermatological concern associated with the overproduction of melanin by human tyrosinase (hsTYR). Despite the existence of many well-known TYR (tyrosinase) inhibitors commercialized in skin formulations, their hsTYR-inhibition efficacy remains poor since most of them were investigated over mushroom tyrosinase (abTYR), a model with low homology relative to hsTYR. Considering the need for new potent hsTYR inhibitors, we designed and synthesized a series of indanones starting from 4-hydroxy compound 1a, one of the two most active derivatives reported to date against the human enzyme, together with marketed thiamidol.

Catechol-mimicking transition-state analogues as non-oxidizable inhibitors of tyrosinases.

Tyrosinases are copper-containing metalloenzymes involved in several processes in both mammals, insects, bacteria, fungi and plants. Their phenol oxidation properties are especially responsible for human melanogenesis, potentially leading to abnormal pigmentation, and for postharvest vegetable tissue browning. Thus, targeting tyrosinases attracts interest for applications both in dermocosmetic and agrofood fields.

An artificial metalloprotein with metal-adaptive coordination sites and Ni-dependent quercetinase activity.

Engineering non-native metal active sites into proteins using canonical amino acids offers many advantages but is hampered by significant challenges. The TIM barrel protein, imidazole glycerol phosphate synthase from the hyperthermophilic organism Thermotoga maritima (tHisF), is well-suited for the construction of artificial metalloenzymes by this approach. To this end, we have generated a tHisF variant (tHisF) with a Glu/His/His motif for metal ion coordination.

Cu -Containing 1-Aminocyclopropane Carboxylic Acid Oxidase Is an Efficient Stereospecific Diels-Alderase.

In the context of developing ecofriendly chemistry, artificial enzymes are now considered as promising tools for synthesis. They are prepared in particular with the aim to catalyze reactions that are rarely, if ever, catalyzed by natural enzymes. We discovered that 1-aminocyclopropane carboxylic acid oxidase reconstituted with Cu served as an efficient artificial Diels-Alderase.