QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton’s tyrosine kinase (BTK) inhibitors
In recent years, there has been a focus on developing and discovering novel Bruton's tyrosine kinase (BTK) inhibitors, as they offer an effective treatment strategy for B-cell malignancies. BTK plays a crucial role in B cell receptor (BCR)-mediated activation and proliferation by regulating dow...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016423004061 |
| _version_ | 1797299712053739520 |
|---|---|
| author | Mourad Aloui Mohammed Er-rajy Hamada Imtara Amina Goudzal Sara Zarougui Mohamed El fadili David E. Arthur Ramzi A. Mothana Omar M. Noman Mahmoud Tarayrah Elhalaoui Menana |
| author_facet | Mourad Aloui Mohammed Er-rajy Hamada Imtara Amina Goudzal Sara Zarougui Mohamed El fadili David E. Arthur Ramzi A. Mothana Omar M. Noman Mahmoud Tarayrah Elhalaoui Menana |
| author_sort | Mourad Aloui |
| collection | DOAJ |
| description | In recent years, there has been a focus on developing and discovering novel Bruton's tyrosine kinase (BTK) inhibitors, as they offer an effective treatment strategy for B-cell malignancies. BTK plays a crucial role in B cell receptor (BCR)-mediated activation and proliferation by regulating downstream factors such as the NF-κB and MAP kinase pathways. To address this challenge and propose potential therapeutic options for B-cell lymphomas, researchers conducted 2D-QSAR and ADMET studies on pyrrolopyrimidine derivatives that act as inhibitors of the BCR site in cytochrome b. These studies aim to improve and identify new compounds that could serve as more potent potential BTK inhibitors, which would lead to the identification of new drug candidates in this field.In our study, we used 2D-QSAR (multiple linear regression, multiple nonlinear regression, and artificial neural networks), molecular docking, molecular dynamics, and ADMET properties to investigate the potential of 35 pyrrolopyrimidine derivatives as BTK inhibitors. A molecular docking study and molecular dynamics simulations of molecule 13 over 10 ns revealed that it establishes multiple hydrogen bonds with several residues and exhibits frequent stability throughout the simulation period. Based on the results obtained by molecular modeling, we proposed six new compounds (Pred1, Pred2, Pred3, Pred4, Pred5, and Pred6) with highly significant predicted activity by MLR models. A study based on the in silico evaluation of the predicted ADMET properties of the new candidate molecules is strongly recommended to classify these molecules as promising candidates for new anticancer agents specifically designed to target Bruton's tyrosine kinase (BTK) inhibition. |
| first_indexed | 2024-03-07T22:55:39Z |
| format | Article |
| id | doaj.art-cb540ee5dbb2472887af86fdeefc4396 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-03-07T22:55:39Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-cb540ee5dbb2472887af86fdeefc43962024-02-23T04:58:42ZengElsevierSaudi Pharmaceutical Journal1319-01642024-01-01321101911QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton’s tyrosine kinase (BTK) inhibitorsMourad Aloui0Mohammed Er-rajy1Hamada Imtara2Amina Goudzal3Sara Zarougui4Mohamed El fadili5David E. Arthur6Ramzi A. Mothana7Omar M. Noman8Mahmoud Tarayrah9Elhalaoui Menana10LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoFaculty of Sciences, Arab American University Palestine, Jenin 44862, Palestine; Corresponding author.Engineering Laboratory of Organometallic, Molecular Materials and Environment, Sidi Mohamed Ben Abdellah University, Faculty of Sciences, Fez, MoroccoLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoDepartment of Pure and Applied Chemistry, University of Maiduguri, NigeriaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaGroupe Hospitalier Cochin-Port Royal, Faculty of Medicine, Institut Cochin, Paris University, CNRS, IN-SERM, 75000, Paris, FranceLIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoIn recent years, there has been a focus on developing and discovering novel Bruton's tyrosine kinase (BTK) inhibitors, as they offer an effective treatment strategy for B-cell malignancies. BTK plays a crucial role in B cell receptor (BCR)-mediated activation and proliferation by regulating downstream factors such as the NF-κB and MAP kinase pathways. To address this challenge and propose potential therapeutic options for B-cell lymphomas, researchers conducted 2D-QSAR and ADMET studies on pyrrolopyrimidine derivatives that act as inhibitors of the BCR site in cytochrome b. These studies aim to improve and identify new compounds that could serve as more potent potential BTK inhibitors, which would lead to the identification of new drug candidates in this field.In our study, we used 2D-QSAR (multiple linear regression, multiple nonlinear regression, and artificial neural networks), molecular docking, molecular dynamics, and ADMET properties to investigate the potential of 35 pyrrolopyrimidine derivatives as BTK inhibitors. A molecular docking study and molecular dynamics simulations of molecule 13 over 10 ns revealed that it establishes multiple hydrogen bonds with several residues and exhibits frequent stability throughout the simulation period. Based on the results obtained by molecular modeling, we proposed six new compounds (Pred1, Pred2, Pred3, Pred4, Pred5, and Pred6) with highly significant predicted activity by MLR models. A study based on the in silico evaluation of the predicted ADMET properties of the new candidate molecules is strongly recommended to classify these molecules as promising candidates for new anticancer agents specifically designed to target Bruton's tyrosine kinase (BTK) inhibition.http://www.sciencedirect.com/science/article/pii/S1319016423004061QSARPyrrolopyrimidineMolecular dockingMolecular dynamicADMET proprietyBTK inhibitors |
| spellingShingle | Mourad Aloui Mohammed Er-rajy Hamada Imtara Amina Goudzal Sara Zarougui Mohamed El fadili David E. Arthur Ramzi A. Mothana Omar M. Noman Mahmoud Tarayrah Elhalaoui Menana QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton’s tyrosine kinase (BTK) inhibitors Saudi Pharmaceutical Journal QSAR Pyrrolopyrimidine Molecular docking Molecular dynamic ADMET propriety BTK inhibitors |
| title | QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton’s tyrosine kinase (BTK) inhibitors |
| title_full | QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton’s tyrosine kinase (BTK) inhibitors |
| title_fullStr | QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton’s tyrosine kinase (BTK) inhibitors |
| title_full_unstemmed | QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton’s tyrosine kinase (BTK) inhibitors |
| title_short | QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton’s tyrosine kinase (BTK) inhibitors |
| title_sort | qsar modelling molecular docking molecular dynamic and admet prediction of pyrrolopyrimidine derivatives as novel bruton s tyrosine kinase btk inhibitors |
| topic | QSAR Pyrrolopyrimidine Molecular docking Molecular dynamic ADMET propriety BTK inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S1319016423004061 |
| work_keys_str_mv | AT mouradaloui qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT mohammederrajy qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT hamadaimtara qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT aminagoudzal qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT sarazarougui qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT mohamedelfadili qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT davidearthur qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT ramziamothana qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT omarmnoman qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT mahmoudtarayrah qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors AT elhalaouimenana qsarmodellingmoleculardockingmoleculardynamicandadmetpredictionofpyrrolopyrimidinederivativesasnovelbrutonstyrosinekinasebtkinhibitors |