Newly Designed Quinazolinone Derivatives as Novel Tyrosinase Inhibitor: Synthesis, Inhibitory Activity, and Mechanism

作者：Huang, Yaru; Yang, Jiefang; Chi, Yunyang; Gong, Chun; Yang, Haikuan; Zeng, Fanxin; Gao, Fang; Hua, Xiaoju; Wang, Zongde^*

来源：MOLECULES, 2022, 27(17): 5558.

DOI：10.3390/molecules27175558

• tyrosinase
• inhibitor
• citral
• derivatives
• fluorescence quenching
• molecular docking

We synthesized a series of quinazolinone derivates as tyrosinase inhibitors and evaluated their inhibition constants. We synthesized 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3H)-one (Q1) from the natural citral. The concentration, which led to 50% activity loss of Q1, was 103 +/- 2 mu M (IC50 = 103 +/- 2 mu M). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the K-I and K-IS inhibition constants to be 117.07 mu M and 423.63 mu M, respectively. Our fluorescence experiment revealed that Q1 could interact with the substrates of tyrosine and L-DOPA in addition to tyrosinase. Molecular docking studies showed that the binding of Q1 to tyrosinase was driven by hydrogen bonding and hydrophobicity. Briefly, the current study confirmed a new tyrosinase inhibitor, which is expected to be developed into a novel pigmentation drug.

• 单位
  江西农业大学