Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation

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Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation Publisher

Mohammadilar F K ; Irajie C ; Sayahi M H ; Moazzam A ; Hashempur M H ; Asadi M ; Larijani B ; Mahdavi M ; Iraji A

Source: European Journal of Medicinal Chemistry Reports Published:2026

Abstract

In this study, rational design and synthesis of a novel series of azobenzene-based derivatives was undertaken, and the optimized derivatives were evaluated for their tyrosinase inhibitory activity. 1H NMR, and 13C NMR, were performed for structural characterization of the synthesized compounds. Among the synthesized compounds, 7b containing a 2-fluorophenyl substituent showed the highest inhibitory activity (IC50 = 13.08 ± 0.53 μM) compared to the standard kojic acid (IC50 = 23.64 ± 2.56 μM). Structure–activity relationship (SAR) analysis demonstrated that ortho-substituted electron-withdrawing groups dramatically increased activity. Kinetic studies using enzymes showed that 7b exhibited competitive inhibition (Ki = 3.76 μM), and docking and MD simulations provided support for strong and stable interactions of the compound with the tyrosinase active site, particularly with histidine residues and Cu2+ ions. Compound 7b also exhibited moderate antioxidant activity in the DPPH assay. These findings suggest that azobenzene-based derivatives, especially compound 7b, can work as tyrosinase inhibitors, holding great promise as potential cosmetic or therapeutic agents in cases of hyperpigmentation. © 2026 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

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Style	Citing Format
MLA	Mohammadilar F K, et al.. "Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation." European Journal of Medicinal Chemistry Reports, vol. 17, no. , 2026, pp. -.
APA	Mohammadilar F K, Irajie C, Sayahi M H, Moazzam A, Hashempur M H, Asadi M, Larijani B, Mahdavi M, Iraji A (2026). Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation. European Journal of Medicinal Chemistry Reports, 17(), -.
Chicago	Mohammadilar F K, Irajie C, Sayahi M H, Moazzam A, Hashempur M H, Asadi M, Larijani B, Mahdavi M, Iraji A. "Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation." European Journal of Medicinal Chemistry Reports 17, no. (2026): -.
Harvard	Mohammadilar F K et al. (2026) 'Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation', European Journal of Medicinal Chemistry Reports, 17(), pp. -.
Vancouver	Mohammadilar F K, Irajie C, Sayahi M H, Moazzam A, Hashempur M H, Asadi M, et al.. Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation. European Journal of Medicinal Chemistry Reports. 2026;17():-.
BibTex	@article{ author = {Mohammadilar F K and Irajie C and Sayahi M H and Moazzam A and Hashempur M H and Asadi M and Larijani B and Mahdavi M and Iraji A}, title = {Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation}, journal = {European Journal of Medicinal Chemistry Reports}, volume = {17}, number = {}, pages = {-}, year = {2026} }
RIS	TY - JOUR AU - Mohammadilar F K AU - Irajie C AU - Sayahi M H AU - Moazzam A AU - Hashempur M H AU - Asadi M AU - Larijani B AU - Mahdavi M AU - Iraji A TI - Azobenzene-Based Derivatives As Tyrosinase Inhibitors: Design, Synthesis, and in Silico Evaluation for Hyperpigmentation JO - European Journal of Medicinal Chemistry Reports VL - 17 IS - SP - EP - PY - 2026 ER -