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

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.

Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances

“…The best activity was displayed by derivative 84a with an IC50 value of 25.48 μM, compared to kojic acid (5, IC50 = 9.30 μM). Also quinazoline derivatives (85-86, Figure 55) were described as TYRIs by Wang et al [100]. Some of the compounds did not show any activity whereas the IC50 values of the active molecules was between 103 and 253 μM, compared to the standard arbutin (6, IC50 = 180 μM).…”

Synthesis and tyrosinase inhibitory activities of novel isopropylquinazolinones

“…Yaru Huang et al reported the synthesis of derivative D with mix type inhibition pattern. Molecular docking studies showed that quinazolinone ring participated in several H-bound interactions with tyrosinase enzyme [ 15 ].…”