Jung Hee Jin, Noh Sang Gyun, Park Yujin, Kang Dongwan, Chun Pusoon, Chung Hae Young, Moon Hyung Ryong
College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
Longevity Life Science and Technology Institutes, Pusan National University, Busan 46241, Republic of Korea.
Comput Struct Biotechnol J. 2019 Aug 1;17:1255-1264. doi: 10.1016/j.csbj.2019.07.017. eCollection 2019.
Tyrosinase is a key enzyme responsible for melanin biosynthesis and is effective in protecting skin damage caused by ultraviolet radiation. As part of ongoing efforts to discover potent tyrosinase inhibitors, we systematically designed and synthesized thirteen ()-benzylidene-1-indanone derivatives (-) and determined their inhibitory activities against tyrosinase. Among the compounds evaluated, was the most potent inhibitor of mushroom tyrosinase (IC = 0.034 µM, monophenolase activity; IC = 1.39 µM, diphenolase activity). Kinetic studies revealed that demonstrated a mixed type of tyrosinase inhibition with value of 2.4 µM using l-DOPA as a substrate. molecular docking simulations demonstrated that can bind to the catalytic and allosteric sites of tyrosinase to inhibit enzyme activity which confirmed experimental studies between and tyrosinase. Furthermore, melanin contents decreased and cellular tyrosinase activity was inhibited after treatment. These observations revealed that is a potent tyrosinase inhibitor and potentially could be used as a whitening agent for the treatment of pigmentation-related disorders.
酪氨酸酶是负责黑色素生物合成的关键酶，对保护皮肤免受紫外线辐射造成的损伤有效。作为发现强效酪氨酸酶抑制剂的持续努力的一部分，我们系统地设计并合成了13种（）-亚苄基-1-茚满酮衍生物（-），并测定了它们对酪氨酸酶的抑制活性。在所评估的化合物中，是蘑菇酪氨酸酶最有效的抑制剂（IC = 0.034 μM，单酚酶活性；IC = 1.39 μM，二酚酶活性）。动力学研究表明，以L-多巴为底物时，表现出混合型酪氨酸酶抑制作用，值为2.4 μM。分子对接模拟表明，可以与酪氨酸酶的催化位点和变构位点结合以抑制酶活性，这证实了与酪氨酸酶之间的实验研究。此外，处理后黑色素含量降低，细胞酪氨酸酶活性受到抑制。这些观察结果表明，是一种强效的酪氨酸酶抑制剂，有可能用作治疗色素沉着相关疾病的美白剂。
