An in-depth study of indolone derivatives as potential lung cancer treatment
Abstract Lung cancer is a type of cancer that begins in the lungs and is one of the leading causes of cancer-related deaths worldwide. Herein an attempt to explore the relationship between the properties of indolone derivatives and their anticancer activity was investigated, implementing in silico a...
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| Format: | Article |
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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/s41598-025-85707-7 |
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| author | Mohammed Er-rajy Mohamed El fadili Radwan Alnajjar Sara Zarougui Somdutt Mujwar Khalil Azzaoui Hatem A. Abuelizz Belkheir Hammouti Menana Elhallaoui |
| author_facet | Mohammed Er-rajy Mohamed El fadili Radwan Alnajjar Sara Zarougui Somdutt Mujwar Khalil Azzaoui Hatem A. Abuelizz Belkheir Hammouti Menana Elhallaoui |
| author_sort | Mohammed Er-rajy |
| collection | DOAJ |
| description | Abstract Lung cancer is a type of cancer that begins in the lungs and is one of the leading causes of cancer-related deaths worldwide. Herein an attempt to explore the relationship between the properties of indolone derivatives and their anticancer activity was investigated, implementing in silico approaches. Four indolone derivatives with the highest anticancer potential were selected to evaluate their pharmacological properties. The ADMET analysis revealed that these compounds exhibited favourable drug-like properties, meeting nearly all the key pharmacological criteria required for potential therapeutic agents. Molecular docking studies of the most active compounds revealed strong interactions with critical amino acid residues in the PDK1 receptor’s binding site, underscoring their potential as effective PDK1 inhibitors. In addition, 200 ns molecular dynamics (MD) simulations of two R and S configurations validated the stability of the ligand-receptor complexes, with minimal structural deviations observed throughout the simulation period. These comprehensive results highlight the potential of the selected indolone derivatives as viable drug candidates and provide a solid foundation for future optimization efforts aimed at developing novel PDK1 inhibitors for cancer therapy. |
| format | Article |
| id | doaj-art-b5ad51fb0f5247a7bba169145abbb35e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b5ad51fb0f5247a7bba169145abbb35e2025-01-19T12:20:16ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85707-7An in-depth study of indolone derivatives as potential lung cancer treatmentMohammed Er-rajy0Mohamed El fadili1Radwan Alnajjar2Sara Zarougui3Somdutt Mujwar4Khalil Azzaoui5Hatem A. Abuelizz6Belkheir Hammouti7Menana Elhallaoui8LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah UniversityLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah UniversityDepartment of Chemistry, Faculty of Science, University of BenghaziLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah UniversityChitkara College of Pharmacy, Chitkara UniversityEngineering Laboratory of Organometallic, Molecular Materials and Environment, Faculty of Sciences, Sidi Mohammed Ben Abdellah UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityEuromed University of Fes, UMFLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah UniversityAbstract Lung cancer is a type of cancer that begins in the lungs and is one of the leading causes of cancer-related deaths worldwide. Herein an attempt to explore the relationship between the properties of indolone derivatives and their anticancer activity was investigated, implementing in silico approaches. Four indolone derivatives with the highest anticancer potential were selected to evaluate their pharmacological properties. The ADMET analysis revealed that these compounds exhibited favourable drug-like properties, meeting nearly all the key pharmacological criteria required for potential therapeutic agents. Molecular docking studies of the most active compounds revealed strong interactions with critical amino acid residues in the PDK1 receptor’s binding site, underscoring their potential as effective PDK1 inhibitors. In addition, 200 ns molecular dynamics (MD) simulations of two R and S configurations validated the stability of the ligand-receptor complexes, with minimal structural deviations observed throughout the simulation period. These comprehensive results highlight the potential of the selected indolone derivatives as viable drug candidates and provide a solid foundation for future optimization efforts aimed at developing novel PDK1 inhibitors for cancer therapy.https://doi.org/10.1038/s41598-025-85707-7PI3K-PDK1-AKT pathwayDFT studyMolecular dockingMolecular dynamicADMET properties |
| spellingShingle | Mohammed Er-rajy Mohamed El fadili Radwan Alnajjar Sara Zarougui Somdutt Mujwar Khalil Azzaoui Hatem A. Abuelizz Belkheir Hammouti Menana Elhallaoui An in-depth study of indolone derivatives as potential lung cancer treatment Scientific Reports PI3K-PDK1-AKT pathway DFT study Molecular docking Molecular dynamic ADMET properties |
| title | An in-depth study of indolone derivatives as potential lung cancer treatment |
| title_full | An in-depth study of indolone derivatives as potential lung cancer treatment |
| title_fullStr | An in-depth study of indolone derivatives as potential lung cancer treatment |
| title_full_unstemmed | An in-depth study of indolone derivatives as potential lung cancer treatment |
| title_short | An in-depth study of indolone derivatives as potential lung cancer treatment |
| title_sort | in depth study of indolone derivatives as potential lung cancer treatment |
| topic | PI3K-PDK1-AKT pathway DFT study Molecular docking Molecular dynamic ADMET properties |
| url | https://doi.org/10.1038/s41598-025-85707-7 |
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