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...

Full description

Saved in:
Bibliographic Details
Main Authors: Mohammed Er-rajy, Mohamed El fadili, Radwan Alnajjar, Sara Zarougui, Somdutt Mujwar, Khalil Azzaoui, Hatem A. Abuelizz, Belkheir Hammouti, Menana Elhallaoui
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-85707-7
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832594788036116480
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
work_keys_str_mv AT mohammederrajy anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT mohamedelfadili anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT radwanalnajjar anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT sarazarougui anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT somduttmujwar anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT khalilazzaoui anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT hatemaabuelizz anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT belkheirhammouti anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT menanaelhallaoui anindepthstudyofindolonederivativesaspotentiallungcancertreatment
AT mohammederrajy indepthstudyofindolonederivativesaspotentiallungcancertreatment
AT mohamedelfadili indepthstudyofindolonederivativesaspotentiallungcancertreatment
AT radwanalnajjar indepthstudyofindolonederivativesaspotentiallungcancertreatment
AT sarazarougui indepthstudyofindolonederivativesaspotentiallungcancertreatment
AT somduttmujwar indepthstudyofindolonederivativesaspotentiallungcancertreatment
AT khalilazzaoui indepthstudyofindolonederivativesaspotentiallungcancertreatment
AT hatemaabuelizz indepthstudyofindolonederivativesaspotentiallungcancertreatment
AT belkheirhammouti indepthstudyofindolonederivativesaspotentiallungcancertreatment
AT menanaelhallaoui indepthstudyofindolonederivativesaspotentiallungcancertreatment