Hydroxylated Coumarin-Based Thiosemicarbazones as Dual Antityrosinase and Antioxidant Agents

Abstract

The design of novel antityrosinase agents appears extremely important in medical and industrial sectors because an irregular production of melanin is related to the insurgence of several skin-related disorders (e.g., melanoma) and the browning process of fruits and vegetables. Because melanogenesis also involves a nonenzymatic oxidative process, developing dual antioxidant and antityrosinase agents is advantageous. In this work, we evaluated the antioxidant and tyrosinase inhibition ability of two new bishydroxylated and two new monohydroxylated derivatives of (1<i>E</i>)-2-(1-(2-oxo-2<i>H</i>-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide (<b>T1</b>) using different experimental and computational approaches. The study was also carried out on another monohydroxylated derivative of <b>T1</b> for comparison. Interestingly, these molecules have more potent tyrosinase-inhibitory properties than the reference compound, kojic acid. Moreover, the antioxidant activity appears to be influenced according to the number and substitution pattern of the hydroxyl groups. The safety of the compounds without (<b>T1</b>), with one (<b>T3</b>), and with two (<b>T6</b>) hydroxyl groups, has also been assessed by studying their cytotoxicity on melanocytes. These results indicate that (1<i>E</i>)-2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide and its hydroxylated derivatives are promising molecules for further drug development studies.