Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B
Aurora kinase B (AKB) is a crucial signaling kinase with an important role in cell division. Therefore, inhibition of AKB is an attractive approach to the treatment of cancer. In the present work, extensive quantitative structure–activity relationships (QSAR) analysis has been performed using a set...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| author | Vijay H. Masand Sami A. Al-Hussain Mithilesh M. Rathore Sumer D. Thakur Siddhartha Akasapu Abdul Samad Aamal A. Al-Mutairi Magdi E. A. Zaki |
| author_facet | Vijay H. Masand Sami A. Al-Hussain Mithilesh M. Rathore Sumer D. Thakur Siddhartha Akasapu Abdul Samad Aamal A. Al-Mutairi Magdi E. A. Zaki |
| author_sort | Vijay H. Masand |
| collection | DOAJ |
| description | Aurora kinase B (AKB) is a crucial signaling kinase with an important role in cell division. Therefore, inhibition of AKB is an attractive approach to the treatment of cancer. In the present work, extensive quantitative structure–activity relationships (QSAR) analysis has been performed using a set of 561 structurally diverse aurora kinase B inhibitors. The Organization for Economic Cooperation and Development (OECD) guidelines were used to develop a QSAR model that has high statistical performance (R<sup>2</sup><sub>tr</sub> = 0.815, Q<sup>2</sup><sub>LMO</sub> = 0.808, R<sup>2</sup><sub>ex</sub> = 0.814, CCC<sub>ex</sub> = 0.899). The seven-variable-based newly developed QSAR model has an excellent balance of external predictive ability (Predictive QSAR) and mechanistic interpretation (Mechanistic QSAR). The QSAR analysis successfully identifies not only the visible pharmacophoric features but also the hidden features. The analysis indicates that the lipophilic and polar groups—especially the H-bond capable groups—must be present at a specific distance from each other. Moreover, the ring nitrogen and ring carbon atoms play important roles in determining the inhibitory activity for AKB. The analysis effectively captures reported as well as unreported pharmacophoric features. The results of the present analysis are also supported by the reported crystal structures of inhibitors bound to AKB. |
| first_indexed | 2024-03-09T17:47:39Z |
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| last_indexed | 2024-03-09T17:47:39Z |
| publishDate | 2022-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9d2145228df445a784c561738b9bfc382023-11-24T11:03:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231452710.3390/ijms232314527Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase BVijay H. Masand0Sami A. Al-Hussain1Mithilesh M. Rathore2Sumer D. Thakur3Siddhartha Akasapu4Abdul Samad5Aamal A. Al-Mutairi6Magdi E. A. Zaki7Department of Chemistry, Vidya Bharati Mahavidyalaya, Amravati 444602, Maharashtra, IndiaDepartment of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi ArabiaDepartment of Chemistry, Vidya Bharati Mahavidyalaya, Amravati 444602, Maharashtra, IndiaDepartment of Chemistry, RDIK and NKD College, Badnera, Amravati 444701, Maharashtra, IndiaCuria Global, Springfield, MO 65807, USADepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Tishk International University, Erbil 44001, IraqDepartment of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh 11623, Saudi ArabiaAurora kinase B (AKB) is a crucial signaling kinase with an important role in cell division. Therefore, inhibition of AKB is an attractive approach to the treatment of cancer. In the present work, extensive quantitative structure–activity relationships (QSAR) analysis has been performed using a set of 561 structurally diverse aurora kinase B inhibitors. The Organization for Economic Cooperation and Development (OECD) guidelines were used to develop a QSAR model that has high statistical performance (R<sup>2</sup><sub>tr</sub> = 0.815, Q<sup>2</sup><sub>LMO</sub> = 0.808, R<sup>2</sup><sub>ex</sub> = 0.814, CCC<sub>ex</sub> = 0.899). The seven-variable-based newly developed QSAR model has an excellent balance of external predictive ability (Predictive QSAR) and mechanistic interpretation (Mechanistic QSAR). The QSAR analysis successfully identifies not only the visible pharmacophoric features but also the hidden features. The analysis indicates that the lipophilic and polar groups—especially the H-bond capable groups—must be present at a specific distance from each other. Moreover, the ring nitrogen and ring carbon atoms play important roles in determining the inhibitory activity for AKB. The analysis effectively captures reported as well as unreported pharmacophoric features. The results of the present analysis are also supported by the reported crystal structures of inhibitors bound to AKB.https://www.mdpi.com/1422-0067/23/23/14527aurora kinase BQSARpharmacophore modeling |
| spellingShingle | Vijay H. Masand Sami A. Al-Hussain Mithilesh M. Rathore Sumer D. Thakur Siddhartha Akasapu Abdul Samad Aamal A. Al-Mutairi Magdi E. A. Zaki Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B International Journal of Molecular Sciences aurora kinase B QSAR pharmacophore modeling |
| title | Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B |
| title_full | Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B |
| title_fullStr | Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B |
| title_full_unstemmed | Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B |
| title_short | Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B |
| title_sort | pharmacophore synergism in diverse scaffold clinches in aurora kinase b |
| topic | aurora kinase B QSAR pharmacophore modeling |
| url | https://www.mdpi.com/1422-0067/23/23/14527 |
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