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
. 2022 Sep 19;23(18):10979.
doi: 10.3390/ijms231810979.

Ultrasonic-Assisted Synthesis of Benzofuran Appended Oxadiazole Molecules as Tyrosinase Inhibitors: Mechanistic Approach through Enzyme Inhibition, Molecular Docking, Chemoinformatics, ADMET and Drug-Likeness Studies

Ali Irfan  1 , Ameer Fawad Zahoor  1 , Shagufta Kamal  2 , Mubashir Hassan  3 , Andrzej Kloczkowski  3   4
Affiliations

Ultrasonic-Assisted Synthesis of Benzofuran Appended Oxadiazole Molecules as Tyrosinase Inhibitors: Mechanistic Approach through Enzyme Inhibition, Molecular Docking, Chemoinformatics, ADMET and Drug-Likeness Studies

Ali Irfan et al. Int J Mol Sci. .

Abstract

Furan-oxadiazole structural hybrids belong to the most promising and biologically active classes of oxygen and nitrogen containing five member heterocycles which have expanded therapeutic scope and potential in the fields of pharmacology, medicinal chemistry and pharmaceutics. A novel series 5a-j of benzofuran-oxadiazole molecules incorporating S-alkylated amide linkage have been synthesized using ultrasonic irradiation and screened for bacterial tyrosinase inhibition activity. Most of the synthesized furan-oxadiazole structural motifs exhibited significant tyrosinase inhibition activity in the micromolar range, with one of the derivatives being more potent than the standard drug ascorbic acid. Among the tested compounds, the scaffold 5a displayed more tyrosinase inhibition efficacy IC50 (11 ± 0.25 μM) than the ascorbic acid IC50 (11.5 ± 0.1 μM). Compounds 5b, 5c and 5d efficiently inhibited bacterial tyrosinase with IC50 values in the range of 12.4 ± 0.0-15.5 ± 0.0 μM. The 2-fluorophenylacetamide containing furan-oxadiazole compound 5a may be considered as a potential lead for tyrosinase inhibition with lesser side effects as a skin whitening and malignant melanoma anticancer agent.

Keywords: ADMET study; chemoinformatics; furan-oxadiazole molecules; molecular docking; structure-activity relationship; tyrosinase inhibitors; ultrasonic-assisted green synthesis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Tyrosinase-catalyzed biosynthesis of melanin.
Figure 2
Figure 2
Clinical drugs with oxadiazole core.
Figure 3
Figure 3
Natural and synthetic furan derivatives.
Scheme 1
Scheme 1
Ultrasonic-assisted synthesis of S-alkylated furan-oxadiazole derivatives 5a–j.
Figure 4
Figure 4
The most biologically active oxadiazole-based furan derivatives 5a–5d as tyrosinase inhibitors.
Figure 5
Figure 5
The structure of bacterial tyrosinase PDB ID 3NM8 (A) and its Ramachandran graph (B).
Figure 6
Figure 6
Binding pocket and interactive behavior of 5a against bacterial tyrosinase (A,B).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zolghadri S., Bahrami A., Hassan Khan Mahmud T., Munoz-Munoz J., Garcia-Molina F., Garcia-Canovas F., Saboury A.A. A comprehensive review on tyrosinaseinhibitors. J. Enzym. Inhib. Med. Chem. 2019;34:279–309. doi: 10.1080/14756366.2018.1545767. - DOI - PMC - PubMed
    1. Nazir Y., Saeed A., Rafiq M., Afzal S., Ali A., Latif M., Zuegg J., Hussein W.M., Fercher C., Barnard R.T., et al. Hydroxyl substituted benzoic acid/cinnamic acid derivatives: Tyrosinase inhibitory kinetics, anti-melanogenic activity and molecular docking studies. Bioorg. Med. Chem. Lett. 2019;30:126722. doi: 10.1016/j.bmcl.2019.126722. - DOI - PubMed
    1. Li J., Feng L., Liu L., Wang F., Ouyang L., Zhang L., Hu X., Wang G. Recent advances in the design and discovery of synthetic tyrosinase inhibitors. Eur. J. Med. Chem. 2021;224:113744. doi: 10.1016/j.ejmech.2021.113744. - DOI - PubMed
    1. Ashraf Z., Rafiq M., Seo S.Y., Kwon K.S., Babar M.M. Kinetic and in silico studies of novel hydroxy-based thymol analogues as inhibitors of mushroom tyrosinase. Eur. J. Med. Chem. 2015;98:203–211. doi: 10.1016/j.ejmech.2015.05.031. - DOI - PubMed
    1. Collins R.P., Warner L.B., Paige L. The Tyrosinase Activity of StrobilomycesStrobilaceus. Mycologia. 1963;55:764–774. doi: 10.1080/00275514.1963.12018067. - DOI

LinkOut - more resources