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Kinetic Studies, Molecular Docking, and Antioxidant Activity of Novel 1,3-Diphenyl Pyrazole-Thiosemicarbazone With Anti-Tyrosinase and Anti-Melanogenesis Properties Publisher Pubmed



Azimi F1 ; Mahdavi M2 ; Khoshneviszadeh M3 ; Shafiee F1 ; Azimi M4 ; Hassanzadeh F1 ; Haji Ashrafee F5
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Authors Affiliations
  1. 1. Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Iran
  2. 2. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  4. 4. Department of Electrical Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran
  5. 5. Hair & Skin Clinic, Persia Delta Teb Clinic, Tehran, Iran

Source: Bioorganic Chemistry Published:2024


Abstract

This study reports the Design Hypothesis of a novel series of 1,3-diphenyl pyrazole-thiosemicarbazone as novel tyrosinase inhibitors (TYRI). The designed compounds were prepared and their TYRI activity and mechanisms were studied. The results showed that the selected compounds exhibited potent tyrosinase inhibitory activities greater than that of kojic acid (KA). Lead candidates, denoted as 6g and 6n, with a para-hydroxyphenyl group attached to the 3-position of the pyrazole ring demonstrated IC50 values of 2.09 and 3.18 µM, respectively. The potency of these compounds was approximately 5–8 times higher than that of KA. The in vitro melanin content of 6g or 6n-treated melanoma cells resulted in significant efficacy in melanin reduction. The DPPH assay result revealed that the tyrosinase inhibition mechanism for these derivatives was independent of a redox effect and corresponded to the interaction with tyrosinase. According to the Lineweaver-Burk plot, the most potent compounds, 6g and 6n, exhibit a mixed type of inhibition, primarily noncompetitive inhibition. In silico molecular docking studies were employed to determine the binding mode and explore the Design Hypothesis in detail. The results suggested that these compounds could be considered promising leads for the further development of novel inhibitors to treat disorders related to tyrosinase. © 2024 Elsevier Inc.
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