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

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.

Automated summary

A series of quinazolinone derivates were synthesized as tyrosinase inhibitors and their inhibition constants were evaluated. The compound 2-(2,6-dimethylhepta-1,5-dien-1-yl)quinazolin-4(3H)-one (Q1) was synthesized from natural citral and exhibited significant inhibitory activity. Q1 was identified as a mixed-type and reversible tyrosinase inhibitor. The study also investigated the binding mechanism of Q1 to tyrosinase and found that Q1 could interact with substrates such as tyrosine and L-DOPA.