Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors
Abstract A series of novel phenylamino quinazolinone derivatives were designed and synthesized as potential tyrosinase inhibitors. Among these compounds, 9r emerged as the most potent derivative, exhibiting IC50 values of 17.02 ± 1.66 µM, compared to kojic acid as the positive control with an IC50 v...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-81328-8 |
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| author | Sara Moghadam Farid Shahram Moradi Dehaghi Aida Iraji Mohammad Mahdavi Mina Saeedi |
| author_facet | Sara Moghadam Farid Shahram Moradi Dehaghi Aida Iraji Mohammad Mahdavi Mina Saeedi |
| author_sort | Sara Moghadam Farid |
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| description | Abstract A series of novel phenylamino quinazolinone derivatives were designed and synthesized as potential tyrosinase inhibitors. Among these compounds, 9r emerged as the most potent derivative, exhibiting IC50 values of 17.02 ± 1.66 µM, compared to kojic acid as the positive control with an IC50 value of 27.56 ± 1.27 µM. Antioxidant assessment of 9r compounds showed 24.67% inhibition at 100 µM. Molecular docking studies of these derivatives were conducted, revealing their proper fitting within the enzyme’s active site. Additionally, density functional theory analysis was performed on the potent derivatives, indicating their stability and reactivity. Notably, the highest values of the energy gap were observed in 9r and 9s derivatives, underscoring their potential efficacy. Further kinetic studies of compound 9r, identified as the most potent derivative, demonstrated a competitive mode of inhibition with a K i value of 14.87 µM. Molecular dynamics simulations of the 9r-tyrosinase complex revealed stability over time, with a reduction in critical residual fluctuation during the simulation. Overall, these findings contribute to a deeper understanding of the potential therapeutic value of these derivatives as tyrosinase inhibitors. |
| format | Article |
| id | doaj-art-7d0a0f3908a74f988973d5221b841a57 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-7d0a0f3908a74f988973d5221b841a572025-01-05T12:17:43ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-024-81328-8Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitorsSara Moghadam Farid0Shahram Moradi Dehaghi1Aida Iraji2Mohammad Mahdavi3Mina Saeedi4Department of Chemistry, North Tehran Branch, Islamic Azad UniversityDepartment of Chemistry, North Tehran Branch, Islamic Azad UniversityDepartment of Persian Medicine, Research Center for Traditional Medicine and History of Medicine, School of Medicine, Shiraz University of Medical SciencesDepartment of Persian Medicine, Research Center for Traditional Medicine and History of Medicine, School of Medicine, Shiraz University of Medical SciencesMedicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical SciencesAbstract A series of novel phenylamino quinazolinone derivatives were designed and synthesized as potential tyrosinase inhibitors. Among these compounds, 9r emerged as the most potent derivative, exhibiting IC50 values of 17.02 ± 1.66 µM, compared to kojic acid as the positive control with an IC50 value of 27.56 ± 1.27 µM. Antioxidant assessment of 9r compounds showed 24.67% inhibition at 100 µM. Molecular docking studies of these derivatives were conducted, revealing their proper fitting within the enzyme’s active site. Additionally, density functional theory analysis was performed on the potent derivatives, indicating their stability and reactivity. Notably, the highest values of the energy gap were observed in 9r and 9s derivatives, underscoring their potential efficacy. Further kinetic studies of compound 9r, identified as the most potent derivative, demonstrated a competitive mode of inhibition with a K i value of 14.87 µM. Molecular dynamics simulations of the 9r-tyrosinase complex revealed stability over time, with a reduction in critical residual fluctuation during the simulation. Overall, these findings contribute to a deeper understanding of the potential therapeutic value of these derivatives as tyrosinase inhibitors.https://doi.org/10.1038/s41598-024-81328-8TyrosinasePhenylamino quinazolinoneMolecular dynamics simulationDFT |
| spellingShingle | Sara Moghadam Farid Shahram Moradi Dehaghi Aida Iraji Mohammad Mahdavi Mina Saeedi Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors Scientific Reports Tyrosinase Phenylamino quinazolinone Molecular dynamics simulation DFT |
| title | Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors |
| title_full | Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors |
| title_fullStr | Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors |
| title_full_unstemmed | Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors |
| title_short | Synthesis, biological evaluations, and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors |
| title_sort | synthesis biological evaluations and in silico assessments of phenylamino quinazolinones as tyrosinase inhibitors |
| topic | Tyrosinase Phenylamino quinazolinone Molecular dynamics simulation DFT |
| url | https://doi.org/10.1038/s41598-024-81328-8 |
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