An in-depth study of indolone derivatives as potential lung cancer treatment
Mohammed Er-Rajy1,2, Mohamed El Fadili3, Radwan Alnajjar4
1LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco. mohammed.errajy@usmba.ac.ma.
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.
Insights
This study explored indolone derivatives as potential lung cancer treatments using computational methods. Promising compounds showed good drug-like properties and effectively inhibited the PDK1 receptor, a key target in cancer therapy.
Area of Science:
- Medicinal Chemistry
- Computational Biology
- Oncology
Background:
- Lung cancer remains a leading cause of cancer mortality globally.
- Identifying novel therapeutic agents is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the relationship between indolone derivative properties and anticancer activity.
- To identify potential drug candidates for lung cancer therapy using in silico approaches.
Main Methods:
- In silico screening of indolone derivatives for anticancer potential.
- ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) analysis to predict pharmacokinetic properties.
- Molecular docking to assess binding affinity with the PDK1 receptor.
- Molecular dynamics simulations to evaluate ligand-receptor complex stability.
Main Results:
- Four indolone derivatives demonstrated significant anticancer potential.
- These compounds exhibited favorable drug-like properties and met key pharmacological criteria.
- Molecular docking revealed strong interactions with critical amino acid residues in the PDK1 receptor.
- Molecular dynamics simulations confirmed the stability of ligand-receptor complexes.
Conclusions:
- The selected indolone derivatives show promise as viable drug candidates for cancer therapy.
- These compounds are potential inhibitors of the PDK1 receptor.
- Further optimization efforts are warranted to develop novel PDK1 inhibitors for lung cancer treatment.
