Background: Tyrosinase enzyme is one of the important targets to reduce melanoma and
other skin disorders. Standard inhibitors of tyrosinase enzyme including arbutin and kojic acid are
less effective. Some NSAIDs such as acetylsalicylic acid, mefanamic acid, and diclofenac are known
to possess inhibitory potential against melanogenesis. The current study deals with the screening of
tyrosinase inhibitory potential of S-naproxen derivatives.
Methods: Synthetic S-naproxen derivatives 1-33 were evaluated for tyrosinase inhibitory activity in
Results: Six compounds 2, 8, 9, 20, 21, and 29 showed good to moderate activity in the range of
(IC50 = 21.05 ± 0.9-53.22 ± 0.7 µM) as compared to the standard kojic acid (IC50 = 16.9 ± 1.3 µM).
Compound 9 (IC50 = 21.05 ± 0.9 µM) was found to be significantly active and showed activity close
to the standard. Compounds 2 (IC50 = 33.23 ± 1.1 µM), 8 (IC50 = 42.10 ± 1.0 µM), 20 (IC50 = 35.40
± 0.4 µM), 21 (IC50 = 41.01 ± 0.6 µM), and 29 (IC50 = 53.22 ± 0.7 µM) were found to be moderately
active. Structure-activity relationship (SAR) was rationalized on the basis of different substituents
and functionalities present on the main scaffold.
Conclusion: This study has identified a number of compounds derived from S-naproxen with
comparable tyrosinase inhibitory activity.