Molecular design of tyrosinase inhibitors: A critical review of promising novel inhibitors from synthetic origins

Abstract

The enzyme tyrosinase is known to be a multifunctional copper-containing enzyme from the oxidase superfamily, which is the key protein involved in the biosynthesis of the large biological pigment, melanin. The enzyme catalyzes two distinct reactions of melanin biosynthesis, the hydroxylation of a monophenol and the conversion of an o-diphenol to the corresponding o-quinone. Inhibitors of this protein have a huge impact on industry and economy. So a number of research groups around the world are engaged and are expending much effort in the discovery of these inhibitors. In this report, we review the importance and applications of the recently designed synthetic tyrosinase inhibitors from our and other leading laboratories of the world, which have been published in recent years. In our continuing search for tyrosinase inhibitors from natural resources to semi-and full synthetic approaches, until now we discovered and reported a large number of mild to potent inhibitors of several classes, such as phenolics, terpenes, steroids, chalcones, flavonoids, alkaloids, long-chain fatty acids, coumarins, sildenafil analogs, bipiperidines, biscoumarins, oxadiazole, tetraketones, etc. The structure-activity relationships (SARs) of different classes of synthetic tyrosinase inhibitors have also been discussed in this review.

Non-specific binding sites help to explain mixed inhibition in mushroom tyrosinase activities

“…Studies on synthetic and natural substances with inhibitory potential have resulted in discovery of some strong inhibitors [3,4], as well as an understanding of some structural requirements for tyrosinase inhibition [3][4][5][6]. In contrast, fewer studies examine the activation of tyrosinase.…”

“…For instance, ethyl and propyl xanthate activated cresolase activity at low concentrations (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) µM) but worked as inhibitors at higher concentrations [17]. In a different study, it was shown that some selected α-keto acids activated catecholase activity but worked as inhibitors in cresolase reaction [18].…”

Synthesis, kinetic mechanism and docking studies of vanillin derivatives as inhibitors of mushroom tyrosinase

“…[10][11][12] A number of researchers reviewed the importance of mushroom tyrosinase, defined its biochemical characteristics and inhibition as well as activation by several inhibitors from natural and synthetic origin for their use in food and cosmetic industry. [13][14][15][16] Tyrosinase is also linked to the sclerotization of cuticle, defensive encapsulation and melanization of foreign organism and wound healing in insects. 17 These biochemical processes offer probable targets for the development of safer and effective tyrosinase inhibitors as insecticides and eventually for insect control.…”

Design, synthesis and bioevaluation of novel umbelliferone analogues as potential mushroom tyrosinase inhibitors

“…Loizzo et al 10 and Chang 11 reviewed the tyrosinase inhibitors from both natural and synthetic origin for their use in food and cosmetic industry. Khan 12 also reviewed the molecular design of tyrosinase inhibitors from synthetic origin.…”