Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors

A library of novel bis-Schiff base derivatives (2a-u) of α-naphthalene moiety was successfully synthesized by four step reactions. Following structural elucidation, these products were evaluated for their in vitro tyrosinase inhibitory potential. In the series, nine derivatives (2e, 2r, 2t, 2 g, 2 u...

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Published in:Journal of Molecular Structure
Main Author: Shah T.A.; Alam A.; Zainab; Khan M.; Elhenawy A.A.; Ayaz M.; Ali M.; Latif A.; Shah S.A.A.; Ahmad M.
Format: Article
Language:English
Published: Elsevier B.V. 2025
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85203657836&doi=10.1016%2fj.molstruc.2024.139919&partnerID=40&md5=4e58ac22f9c4328158be78eebaece9b4
id 2-s2.0-85203657836
spelling 2-s2.0-85203657836
Shah T.A.; Alam A.; Zainab; Khan M.; Elhenawy A.A.; Ayaz M.; Ali M.; Latif A.; Shah S.A.A.; Ahmad M.
Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors
2025
Journal of Molecular Structure
1321

10.1016/j.molstruc.2024.139919
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85203657836&doi=10.1016%2fj.molstruc.2024.139919&partnerID=40&md5=4e58ac22f9c4328158be78eebaece9b4
A library of novel bis-Schiff base derivatives (2a-u) of α-naphthalene moiety was successfully synthesized by four step reactions. Following structural elucidation, these products were evaluated for their in vitro tyrosinase inhibitory potential. In the series, nine derivatives (2e, 2r, 2t, 2 g, 2 u, 2p, 2a, 2d, and 2 h) attributed excellent inhibitory activity in the range of IC50 values from 2.3 ± 1.7 to 17.6 ± 0.9 µM superior to the standard drug kojic acid. Similarly, four compounds showed significant activities near to the standard while the remaining eight compounds displayed good to moderate inhibition with IC50 values from 29.3 ± 2.9 to 63.2 ± 1.1 µM. The molecular docking investigations for most active compounds (2e, 2r, 2t, 2 g, 2 u, 2p, 2a, 2d, and 2 h) form high stability in binding site of the tyrosinase active site, than standard kojic acid. Frontier molecular orbitals, such as HOMO and LUMO to show the charge transfer from molecule to biological medium and MEP map to show the chemically reactive zone appropriate for drug action, are calculated using TD-DFT. Besides, the drug-likeness prediction showed that these compounds showed a desirable property, such as high intestinal absorption, large volume of distribution, good BBB penetration, and low toxicity. These bis-Schiff bases have a high oral bioavailability, which can categorized as a unique drug candidate in future. © 2024 Elsevier B.V.
Elsevier B.V.
222860
English
Article

author Shah T.A.; Alam A.; Zainab; Khan M.; Elhenawy A.A.; Ayaz M.; Ali M.; Latif A.; Shah S.A.A.; Ahmad M.
spellingShingle Shah T.A.; Alam A.; Zainab; Khan M.; Elhenawy A.A.; Ayaz M.; Ali M.; Latif A.; Shah S.A.A.; Ahmad M.
Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors
author_facet Shah T.A.; Alam A.; Zainab; Khan M.; Elhenawy A.A.; Ayaz M.; Ali M.; Latif A.; Shah S.A.A.; Ahmad M.
author_sort Shah T.A.; Alam A.; Zainab; Khan M.; Elhenawy A.A.; Ayaz M.; Ali M.; Latif A.; Shah S.A.A.; Ahmad M.
title Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors
title_short Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors
title_full Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors
title_fullStr Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors
title_full_unstemmed Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors
title_sort Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors
publishDate 2025
container_title Journal of Molecular Structure
container_volume 1321
container_issue
doi_str_mv 10.1016/j.molstruc.2024.139919
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-85203657836&doi=10.1016%2fj.molstruc.2024.139919&partnerID=40&md5=4e58ac22f9c4328158be78eebaece9b4
description A library of novel bis-Schiff base derivatives (2a-u) of α-naphthalene moiety was successfully synthesized by four step reactions. Following structural elucidation, these products were evaluated for their in vitro tyrosinase inhibitory potential. In the series, nine derivatives (2e, 2r, 2t, 2 g, 2 u, 2p, 2a, 2d, and 2 h) attributed excellent inhibitory activity in the range of IC50 values from 2.3 ± 1.7 to 17.6 ± 0.9 µM superior to the standard drug kojic acid. Similarly, four compounds showed significant activities near to the standard while the remaining eight compounds displayed good to moderate inhibition with IC50 values from 29.3 ± 2.9 to 63.2 ± 1.1 µM. The molecular docking investigations for most active compounds (2e, 2r, 2t, 2 g, 2 u, 2p, 2a, 2d, and 2 h) form high stability in binding site of the tyrosinase active site, than standard kojic acid. Frontier molecular orbitals, such as HOMO and LUMO to show the charge transfer from molecule to biological medium and MEP map to show the chemically reactive zone appropriate for drug action, are calculated using TD-DFT. Besides, the drug-likeness prediction showed that these compounds showed a desirable property, such as high intestinal absorption, large volume of distribution, good BBB penetration, and low toxicity. These bis-Schiff bases have a high oral bioavailability, which can categorized as a unique drug candidate in future. © 2024 Elsevier B.V.
publisher Elsevier B.V.
issn 222860
language English
format Article
accesstype
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