Yousefi, R. (2025). A Molecular Docking Study Conducted on the Model of Tyrosinase-Related Protein 1 from (PDB ID: 5M8T) Using Kojic Acid and Its Structural Analogs as Inhibitors. Journal of Advanced Pharmacy Research, 9(1), 41-61. doi: 10.21608/aprh.2024.310212.1286
Roohallah Yousefi. "A Molecular Docking Study Conducted on the Model of Tyrosinase-Related Protein 1 from (PDB ID: 5M8T) Using Kojic Acid and Its Structural Analogs as Inhibitors". Journal of Advanced Pharmacy Research, 9, 1, 2025, 41-61. doi: 10.21608/aprh.2024.310212.1286
Yousefi, R. (2025). 'A Molecular Docking Study Conducted on the Model of Tyrosinase-Related Protein 1 from (PDB ID: 5M8T) Using Kojic Acid and Its Structural Analogs as Inhibitors', Journal of Advanced Pharmacy Research, 9(1), pp. 41-61. doi: 10.21608/aprh.2024.310212.1286
Yousefi, R. A Molecular Docking Study Conducted on the Model of Tyrosinase-Related Protein 1 from (PDB ID: 5M8T) Using Kojic Acid and Its Structural Analogs as Inhibitors. Journal of Advanced Pharmacy Research, 2025; 9(1): 41-61. doi: 10.21608/aprh.2024.310212.1286
A Molecular Docking Study Conducted on the Model of Tyrosinase-Related Protein 1 from (PDB ID: 5M8T) Using Kojic Acid and Its Structural Analogs as Inhibitors
1Behbahan Faculty of Medical Sciences, Behbahan, Iran.
2Department of Biochemistry, Faculty of Biology, Tarbit Modares University, Tehran, Iran.
Abstract
Background: Kojic acid and its related compounds, such as β-arbutin, α-arbutin, and deoxyarbutin, are known for inhibiting tyrosinase activity, which is crucial for melanin production in the skin. Kojic acid acts as a chelating agent that binds to copper ions in tyrosinase, inhibiting its activity. β-arbutin and α-arbutin are natural compounds that competitively inhibit tyrosinase by releasing hydroquinone upon absorption into the skin. Deoxyarbutin, a synthetic derivative, is a potent inhibitor of tyrosinase due to its stability and ability to bind to copper ions, preventing the oxidation of tyrosine and DOPA. These compounds effectively reduce melanin production, resulting in a lighter complexion by interfering with the melanin synthesis pathway through tyrosinase inhibition. Objectives: In the present study, we investigate the affinity of binding and binding site of kojic acid and its analogues for the inhibition of tyrosinase-related protein 1. Methods: In this study, we utilized the tyrosinase-related protein 1 (TYRP1) model from the Protein Data Bank (PDB) with the [PDB ID: 5M8T]. Molecular docking was performed using the Molegro Virtual Docker tool with models of 22 ligand compounds from the PubChem database, including kojic acid and its analogues. The physicochemical properties and pharmacokinetics of the compounds were predicted using the SwissADME web tool. Results: Our study identified various binding sites of kojic acid and its analogues on TRP1, which included amino acids such as Gln78, Gly209, Glu210, Val211, Asp212, Phe213, His215, Glu216, Tyr348, Ser349, Pro431, Ile432, and His434. These compounds showed high gastrointestinal absorption, inability to cross the blood-brain barrier, no inhibition of cytochrome P450 enzymes, and not being Pgp substrates. Additionally, they exhibited minimal skin absorption. Discussion: Our study examined 22 analog compounds of kojic acid, which exhibited high gastrointestinal absorption but lacked permeability through the blood-brain barrier. All of the studied compounds, consisting of Kojic acid and β-arbutin, exhibit effective binding affinity and binding sites for the inhibition of TYRP1. Conclusion: This study provides evidence supporting the effectiveness of kojic acid and its similar compounds in inhibiting TYRP1 activity, which could be valuable in the treatment of skin conditions related to hyperpigmentation.
Methods and Materials: In this study, we utilized the tyrosinase-related protein 1 (TYRP1) model from the Protein Data Bank (PDB) with the [PDB ID: 5M8T]. Molecular docking was performed using the Molegro Virtual Docker tool with models of 22 ligand compounds from the PubChem database, including kojic acid and its analogs. The physicochemical properties and pharmacokinetics of the compounds were predicted using the SwissADME web tool. Results: Our study identified various binding sites of kojic acid and its analogs on TRP1, which included amino acids such as Gln78, Gly209, Glu210, Val211, Asp212, Phe213, His215, Glu216, Tyr348, Ser349, Pro431, Ile432, and His434. These compounds showed high gastrointestinal absorption, inability to cross the blood-brain barrier, no inhibition of cytochrome P450 enzymes, and not being Pgp substrates. Additionally, they exhibited minimal skin absorption. Discussion: Our study examined 22 analog compounds of kojic acid, which exhibited high gastrointestinal absorption but lacked permeability through the blood-brain barrier. All of the studied compounds, consisting of Kojic acid and β-arbutin, exhibit effective binding affinity and binding sites for the inhibition of TYRP1. Conclusion: This study provides evidence supporting the effectiveness of kojic acid and its similar compounds in inhibiting TYRP1 activity, which could be valuable in the treatment of skin conditions related to hyperpigmentation.
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