Masuri Sebastiano, Era Benedetta, Pintus Francesca, Floris Sonia, Meloni Francesca, Pettinau Francesca, Podda Enrico, Cabiddu Maria Grazia, Fais Antonella, Pivetta Tiziana
Department of Chemical and Geological Sciences, University of Cagliari, S.S. 554 Bivio Sestu, Monserrato, 09042 Cagliari, Italy.
Department of Life and Environmental Sciences, University of Cagliari, S.S. 554 Bivio Sestu, Monserrato, 09042 Cagliari, Italy.
Molecules. 2024 Nov 28;29(23):5629. doi: 10.3390/molecules29235629.
Tyrosinase, a key protein in the biosynthesis of melanin pigments, is crucial in determining skin pigmentation. Inhibiting tyrosinase activity is a promising approach for treating conditions related to excessive pigmentation. For the synthesis of more potent tyrosinase inhibitors, we combined two approaches, para-substitution and lipophilicity, to enhance the inhibitory properties of ()-2-(4-hydroxybenzylidene)hydrazine-1-carbotiamide, whose enzyme inhibitory properties have been previously demonstrated. The newly synthesized compounds showed potent inhibition activity against tyrosinase in the micromolar concentration range. The synthesised compounds were up to 41 times more effective than kojic acid. In addition to this biological activity, all molecules were evaluated for their sun protection factor to determine their photoprotective effects. All the compounds showed higher efficacy than reference compounds, used as sunscreens in photoprotective preparations. All compounds were noncytotoxic at the concentration required to inhibit tyrosinase activity. With the aim of defining the potential binding modes and the kind of interactions between the studied molecules and the catalytic site of mushroom tyrosinase, molecular docking simulations were also performed.
酪氨酸酶是黑色素生物合成中的关键蛋白，对决定皮肤色素沉着至关重要。抑制酪氨酸酶活性是治疗与色素沉着过多相关病症的一种有前景的方法。为了合成更有效的酪氨酸酶抑制剂，我们结合了对位取代和亲脂性这两种方法，以增强（）-2-（4-羟基亚苄基）肼-1-碳硫酰胺的抑制特性，其酶抑制特性先前已得到证实。新合成的化合物在微摩尔浓度范围内对酪氨酸酶表现出强效抑制活性。合成的化合物比曲酸有效高达41倍。除了这种生物活性外，还对所有分子的防晒系数进行了评估，以确定它们的光保护作用。所有化合物均显示出比用作光保护制剂中防晒剂的参考化合物更高的功效。所有化合物在抑制酪氨酸酶活性所需的浓度下均无细胞毒性。为了确定所研究分子与蘑菇酪氨酸酶催化位点之间的潜在结合模式和相互作用类型，还进行了分子对接模拟。
