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. 2022 Aug 29;27(17):5558.
doi: 10.3390/molecules27175558.

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

Yaru Huang  1 , Jiefang Yang  2 , Yunyang Chi  2 , Chun Gong  2 , Haikuan Yang  2 , Fanxin Zeng  2 , Fang Gao  3 , Xiaoju Hua  2 , Zongde Wang  1
Affiliations

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

Yaru Huang et al. Molecules. .

Abstract

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 μM (IC50 = 103 ± 2 μM). Furthermore, we considered Q1 to be a mixed-type and reversible tyrosinase inhibitor, and determined the KI and KIS inhibition constants to be 117.07 μM and 423.63 μM, 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.

Keywords: citral; derivatives; fluorescence quenching; inhibitor; molecular docking; tyrosinase.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Inhibitory effect of Q1 (curve 1) and arbutin (curve 2) on mushroom tyrosinase.
Figure 2
Figure 2
Remaining mushroom tyrosinase activity at different concentrations of Q1. Concentrations of Q1 for curves 1–4 were 0, 15, 60, 120 µM.
Figure 3
Figure 3
Kinetic parameters of mushroom tyrosinase inhibition by Q1. Concentrations of Q1 for curves 1–4 were 0, 15, 60, 120 µM.
Figure 4
Figure 4
Fluorescence emission spectra of mushroom tyrosinase solution in presence of Q1 with different concentrations. Curves 0–4 representing concentrations of Q1 are 0, 9, 18, 27, 36 μM; curve A is fluorescence emission spectra of Q1 at concentration of 36 μM.
Figure 5
Figure 5
Fluorescence emission spectra of tyrosine solution in presence of Q1 with different concentrations. Concentrations of samples for curves 0–4 are 0, 9, 18, 27, 36 μM. Curve A is fluorescence emission spectra of Q1 at concentration of 36 μM.
Figure 6
Figure 6
Fluorescence emission spectra of L-DOPA solution in presence of Q1 with different concentrations. Concentrations of samples for curves 0–4 are 0, 9, 18, 27, 36 μM. Curve A is fluorescence emission spectra of Q1 at concentration of 36 μM.
Figure 7
Figure 7
Molecular docking result of Q1 with mushroom tyrosinase.
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