BENZYLIDENANILINES AND RELATED COMPOUNDS AS TYROSINASE INHIBITORS

Abstract

Excessive accumulation of melanin leads to a number of skin diseases and cosmetic problems, namely toxic and medicinal melanoderma, melasma, lentigo, etc. The leading role in the formation of melanin belongs to tyrosinase, an enzyme of the class of oxidoreductases (ЕС 1.14.18.1), which catalyzes the first stages of pigment formation. Therefore, to prevent or treat hyperpigmentation of the skin, agents containing tyrosinase inhibitors, are used. To date, many inhibitors of enzyme are known. However, existing compounds have significant drawbacks, such as instability, inefficiency, toxicity, complex methods of synthesis or isolation from natural sources. The aim of this work was to study benzylidenaniline, its derivatives and related compounds as tyrosinase inhibitors. It was shown that benzylidene-2-aminophenol and benzylidene-4-aminophenol are effective inhibitors of tyrosinase monophenolase activity (IC50 of 7.8 and 31.2 μmol/dm3, respectively) and significantly exceeds the standard inhibitor - kojic acid by inhibitory ability. It was found, that benzylideneanilines studied reduced only the monophenolase activity enzyme and did not affect the diphenolase activity. It was found, that unsubstituted benzylideniline is also a tyrosinase inhibitor (IC50 110.4 μmol/dm3), although it is significantly inferior in efficiency to hydroxy derivatives and kojic acid. The influence of other aldimines on enzyme activity was studied. It has been shown that compounds, containing a naphthalene fragment, a heteroatom in the aniline ring, and a carbon bridge between the aromatic rings are not tyrosinase inhibitors. It was found, that 3-(2-hydroxyphenylimino)-1,3-dihydroindol-2-one exhibited a significant inhibitory ability (8.8 μmol/dm3) close to such of benzylidene-2-aminophenol.