Azizeh Asadzadeh - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Hajar Sirous - Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
Morteza Pourfarzam - Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
Parichehreh Yaghmaei - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
Afshin Fassihi - Department of Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Objective(s): Tyrosinase is a key enzyme in pigment synthesis. Overproduction of melanin in parts of the skin results in hyperpigmentation diseases. This enzyme is also responsible for the enzymatic browning in fruits and vegetables. Thus, its inhibitors are of great importance in the medical, cosmetic and agricultural fields. Materials and Methods: A series of twelve kojic acid derivatives were designed to be evaluated as tyrosinase activity inhibitors. The potential inhibitory activity of these compounds was investigated in silico using molecular docking simulation method. Four compounds with a range of predicted tyrosinase inhibitory activities were prepared and their inhibitory effect on tyrosinase activity was evaluated. The antioxidant properties of these compounds were also investigated by in vitro DPPH (۲,۲-diphenyl-۱-picrylhydrazyl) and hydrogen peroxide scavenging assays. Results: Compound IIId exhibited the highest tyrosinase inhibitory activity with an IC۵۰ value of ۰.۲۱۶ ± ۰.۰۰۹ mM which was in accordance with the in silico ΔGbind results (-۱۳.۲۴ Kcal/mol). Conclusion: Based on the docking studies, from the twelve compounds studied, one (IIId) appeared to have the highest inhibition on tyrosinase activity. This was confirmed by enzyme activity measurements. Compound IIId has an NO۲ group which binds to both of Cu۲+ ions located inside the active site of the enzyme. This compound appeared to be even stronger than kojic acid in inhibiting tyrosinase activity. The DPPH free radical scavenging ability of all the studied compounds was more than that of BHT. However, they were not as strong as BHT or gallic acid in scavenging hydrogen peroxide.

Antioxidant activity, In silico studies, Kojic acid, Tyrosinase