Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 23;17(1):65.
doi: 10.1186/s13065-023-00978-3.

Synthesis and tyrosinase inhibitory activities of novel isopropylquinazolinones

Arshia Hashemi  1 , Milad Noori  2   3 , Navid Dastyafteh  2 , Seyed Esmaeil Sadat-Ebrahimi  1 , Negin Fazelzadeh Haghighi  4 , Katayoun Mehrpour  3   5 , Elahe Sattarinezhad  6 , Fatemeh Jalali Zafrei  7 , Cambyz Irajie  8 , Mohammad Ali Daneshmehr  1 , Majid Heydari  9 , Bagher Larijani  2 , Aida Iraji  10   11 , Mohammad Mahdavi  12
Affiliations

Synthesis and tyrosinase inhibitory activities of novel isopropylquinazolinones

Arshia Hashemi et al. BMC Chem. .

Abstract

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 µM. 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 µM, 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.

Keywords: Enzyme inhibition; In silico studies; Isopropylquinazolinone; Kinetic evaluation; Synthesise; Tyrosinase.

PubMed Disclaimer

Conflict of interest statement

Not applicable.

Figures

Fig. 1
Fig. 1
Chemical structures of some reported tyrosinase inhibitors and newly designed compound
Scheme 1
Scheme 1
Synthesis of isopropylquinazolinone derivatives 9a–q
Fig. 2
Fig. 2
Kinetics of tyrosinase inhibition by 9q. a The Lineweaver–Burk plot in the absence and presence of different concentrations of 9q; b The secondary plot of slopes of the lines vs various concentrations of 9q; c The secondary plot of 1/Vmax vs various concentrations of 9q
Fig. 3
Fig. 3
3D and 2D diagrams of compound 9q within the binding pocket of tyrosinase
See this image and copyright information in PMC

References

    1. Sepehri N, Iraji A, Yavari A, Asgari MS, Zamani S, Hosseini S, Bahadorikhalili S, Pirhadi S, Larijani B, Khoshneviszadeh M. The natural-based optimization of kojic acid conjugated to different thio-quinazolinones as potential anti-melanogenesis agents with tyrosinase inhibitory activity. Bioorg Med Chem. 2021;36:116044. doi: 10.1016/j.bmc.2021.116044. - DOI - PubMed
    1. Hosseinpoor H, Farid SM, Iraji A, Askari S, Edraki N, Hosseini S, Jamshidzadeh A, Larijani B, Attarroshan M, Pirhadi S. Anti-melanogenesis and anti-tyrosinase properties of aryl-substituted acetamides of phenoxy methyl triazole conjugated with thiosemicarbazide: design, synthesis and biological evaluations. Bioorg Chem. 2021;114:104979. doi: 10.1016/j.bioorg.2021.104979. - DOI - PubMed
    1. Iraji A, Adelpour T, Edraki N, Khoshneviszadeh M, Miri R, Khoshneviszadeh M. Synthesis, biological evaluation and molecular docking analysis of vaniline–benzylidenehydrazine hybrids as potent tyrosinase inhibitors. BMC Chem. 2020;14(1):28. doi: 10.1186/s13065-020-00679-1. - DOI - PMC - PubMed
    1. Karimian S, Kazemi F, Attarroshan M, Gholampour M, Hemmati S, Sakhteman A, Behzadipour Y, Kabiri M, Iraji A, Khoshneviszadeh M. Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors. BMC Chem. 2021;15(1):54. doi: 10.1186/s13065-021-00780-z. - DOI - PMC - PubMed
    1. Karimian S, Kazemi F, Attarroshan M, Gholampour M, Hemmati S, Sakhteman A, Behzadipour Y, Kabiri M, Iraji A, Khoshneviszadeh M. Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors. BMC Chem. 2021;15(1):1–11. doi: 10.1186/s13065-021-00780-z. - DOI - PMC - PubMed

LinkOut - more resources