Calixbenoquin: Calixarene-Based Cluster of Monobenzone as a New Anti-Tyrosinase Agent.

Tyrosinase, copper-containing glycoprotein, is a key enzyme in the biosynthesis of melanin pigment from L-tyrosine. The excessive production of melanin in the skin due to skin disorders, such as melasma, is of great importance. Therefore, tyrosinase inhibitors are used for treatments of them. One of these inhibitors is monobenzone (benoquin) as a skin whitening agent, which has a phenolic structure. The phenolic structure of this drug, prompted the author to design its novel calix[4]arene-based cluster in a chalice-shaped structure. Therefore, the present study reports the synthesis and in vitro anti-tyrosinase of the chalice-shaped cluster of benoquin (namely calixbenoquin) in comparison to its simple drug unit (benoquin) as the reference medication. The synthetic route included chemical modification of the calix[4]arene structure by grafting four hydroxyl and benzyloxy groups on the upper and the lower rim of the calix[4]arene scaffold, respectively. The in vitro biological results showed an enhanced (about 4.5-fold) anti-tyrosinase activity for the calixarene-based cluster (calixbenoquin) in relation to its phenolic monomer (benoquin). Therefore, compared to benoquin, calixbenoquin with improved bioactivity can be considered as a new melanogenesis inhibitor with low dose range. These improved pharmaceutical effects are probably attributed to the clustering effect and improved interaction of four impacted benoquin units of the cluster with the active site of tyrosinase. [ABSTRACT FROM AUTHOR]