Synthesis and tyrosinase inhibitory activities of novel isopropylquinazolinones

To find new anti-browning and whitening agents in this study, new series of isopropylquinazolinone derivatives were designed and synthesized. All derivatives were evaluated as possible tyrosinase inhibitors and compound 9q bearing 4-fluorobenzyl moieties at the R position exhibited the best potencies with an IC50 value of 34.67 +/- 3.68 mu M. The kinetic evaluations of 9q as the most potent derivatives recorded mix-type inhibition. Compounds 9o and 9q also exhibited potent antioxidant capacity with IC50 values of 38.81 and 40.73 mu M, respectively confirming their antioxidant potential. Molecular docking studies of 9q as the most potent derivative were exacuated and it was shown that quinazolinone and acetamide moieties of compound 9q participated in interaction with critical His residues of the binding site. The obtained results demonstrated that the 9q can be considered a suitable pharmacophore to develop potent tyrosinase inhibitors.

Automated summary

In this study, new series of isopropylquinazolinone derivatives were designed and synthesized to discover new anti-browning and whitening agents. Compound 9q, with 4-fluorobenzyl moieties at the R position, exhibited the most potent inhibitory activity against tyrosinase with an IC50 value of 34.67 +/- 3.68 mu M. Kinetic evaluations revealed that compound 9q had mix-type inhibition. Additionally, compounds 9o and 9q demonstrated strong antioxidant capacity, confirming their potential as antioxidants. Molecular docking studies of compound 9q showed that its quinazolinone and acetamide moieties interacted with critical His residues in the binding site. These results suggest that 9q could be a suitable pharmacophore for developing potent tyrosinase inhibitors.