2D-QSAR and docking study of a series of coumarin derivatives as inhibitors of CDK (anticancer activity) with an application of the molecular docking method
Quantitative Structure Activity Relationship (QSAR) analysis techniques are tools largely utilized in many research fields, including drug discovery processes.In this work electronic descriptors are calculated with the Gaussian 03W software using the DFT method with the BecKe 3-parameters exchange f...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-08-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402031358X |
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| author | Rania Kasmi Elghalia Hadaji Oussama Chedadi Abdellah El Aissouq Mohammed Bouachrine Abdelkrim Ouammou |
| author_facet | Rania Kasmi Elghalia Hadaji Oussama Chedadi Abdellah El Aissouq Mohammed Bouachrine Abdelkrim Ouammou |
| author_sort | Rania Kasmi |
| collection | DOAJ |
| description | Quantitative Structure Activity Relationship (QSAR) analysis techniques are tools largely utilized in many research fields, including drug discovery processes.In this work electronic descriptors are calculated with the Gaussian 03W software using the DFT method with the BecKe 3-parameters exchange functional and Lee-Yang-Parr correlation functional, with Kohn and Sham orbitals (KS) developed on a Gaussian Basis of type 6-31G (d), in combination with five Lipinski parameters that have been calculated with ChemOffice software, in order to develop a statistically verified 2D-QSAR model able to predict the biological activity of new molecules belonging to the same range of coumarins rather than chemical synthesis and biological evaluations that require more time and resources. Two QSAR models against both MCF-7 and HepG-2 cell lines are obtained using the multiple linear regression method.The predictive power of these models has been confirmed by internal and external validation. The Leverage method was used to determine the domain of applicability of the 2D-QSAR models developed. The results indicate that the best QSAR model is the one that links the 2D descriptors with the CDK inhibitory activity of the cell line (HepG-2) R2 = 0.748, R2cv = 0.618, MSE = 0.03 for the learning series and R2 = 0.73, MSE = 0.18 for the test series. This model implies that coumarin inhibitory activity is strongly related to dipole moment and the number of hydrogen bond donors. The results obtained suggest the importance of studying structure-activity relationships as a principal axis in drug design. The docking procedure using AutoDOCK Tools was also used to understand the mechanisms of molecular interactions and consequently, to develop new inhibitors. |
| first_indexed | 2024-12-12T05:04:14Z |
| format | Article |
| id | doaj.art-5c7c03c83ec5476f9d72602c876fe818 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-12T05:04:14Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-5c7c03c83ec5476f9d72602c876fe8182022-12-22T00:37:08ZengElsevierHeliyon2405-84402020-08-0168e045142D-QSAR and docking study of a series of coumarin derivatives as inhibitors of CDK (anticancer activity) with an application of the molecular docking methodRania Kasmi0Elghalia Hadaji1Oussama Chedadi2Abdellah El Aissouq3Mohammed Bouachrine4Abdelkrim Ouammou5LIMOME Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoLIMOME Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco; Corresponding author.LIMOME Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoLIMOME Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoMCNS Laboratory, Faculty of Science, University Moulay Ismail, Meknes, Morocco; EST Khenifra, Sultan Moulay Sliman University, MoroccoLIMOME Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, MoroccoQuantitative Structure Activity Relationship (QSAR) analysis techniques are tools largely utilized in many research fields, including drug discovery processes.In this work electronic descriptors are calculated with the Gaussian 03W software using the DFT method with the BecKe 3-parameters exchange functional and Lee-Yang-Parr correlation functional, with Kohn and Sham orbitals (KS) developed on a Gaussian Basis of type 6-31G (d), in combination with five Lipinski parameters that have been calculated with ChemOffice software, in order to develop a statistically verified 2D-QSAR model able to predict the biological activity of new molecules belonging to the same range of coumarins rather than chemical synthesis and biological evaluations that require more time and resources. Two QSAR models against both MCF-7 and HepG-2 cell lines are obtained using the multiple linear regression method.The predictive power of these models has been confirmed by internal and external validation. The Leverage method was used to determine the domain of applicability of the 2D-QSAR models developed. The results indicate that the best QSAR model is the one that links the 2D descriptors with the CDK inhibitory activity of the cell line (HepG-2) R2 = 0.748, R2cv = 0.618, MSE = 0.03 for the learning series and R2 = 0.73, MSE = 0.18 for the test series. This model implies that coumarin inhibitory activity is strongly related to dipole moment and the number of hydrogen bond donors. The results obtained suggest the importance of studying structure-activity relationships as a principal axis in drug design. The docking procedure using AutoDOCK Tools was also used to understand the mechanisms of molecular interactions and consequently, to develop new inhibitors.http://www.sciencedirect.com/science/article/pii/S240584402031358XPharmaceutical chemistryTheoretical chemistryDFTCoumarinMLRValidation |
| spellingShingle | Rania Kasmi Elghalia Hadaji Oussama Chedadi Abdellah El Aissouq Mohammed Bouachrine Abdelkrim Ouammou 2D-QSAR and docking study of a series of coumarin derivatives as inhibitors of CDK (anticancer activity) with an application of the molecular docking method Heliyon Pharmaceutical chemistry Theoretical chemistry DFT Coumarin MLR Validation |
| title | 2D-QSAR and docking study of a series of coumarin derivatives as inhibitors of CDK (anticancer activity) with an application of the molecular docking method |
| title_full | 2D-QSAR and docking study of a series of coumarin derivatives as inhibitors of CDK (anticancer activity) with an application of the molecular docking method |
| title_fullStr | 2D-QSAR and docking study of a series of coumarin derivatives as inhibitors of CDK (anticancer activity) with an application of the molecular docking method |
| title_full_unstemmed | 2D-QSAR and docking study of a series of coumarin derivatives as inhibitors of CDK (anticancer activity) with an application of the molecular docking method |
| title_short | 2D-QSAR and docking study of a series of coumarin derivatives as inhibitors of CDK (anticancer activity) with an application of the molecular docking method |
| title_sort | 2d qsar and docking study of a series of coumarin derivatives as inhibitors of cdk anticancer activity with an application of the molecular docking method |
| topic | Pharmaceutical chemistry Theoretical chemistry DFT Coumarin MLR Validation |
| url | http://www.sciencedirect.com/science/article/pii/S240584402031358X |
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