3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors
Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhib...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Published: |
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/18615 |
| _version_ | 1848749796187176960 |
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| author | Arooj, Mahreen Thangapandian, S. John, S. Hwang, S. Park, J. Lee, K. |
| author_facet | Arooj, Mahreen Thangapandian, S. John, S. Hwang, S. Park, J. Lee, K. |
| author_sort | Arooj, Mahreen |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed. A highly correlating (r = 0.942) pharmacophore model (Hypo1) with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated. After successfully validating "Hypo1", it is further applied in database screening. Hit compounds are subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits. Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC 50) data thus successfully validating "Hypo1" by DFT method. Therefore, this research exertion can be helpful in the development of new potent hits for chymase. In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors. © 2011 by the authors; licensee MDPI, Basel, Switzerland. |
| first_indexed | 2025-11-14T07:26:38Z |
| format | Journal Article |
| id | curtin-20.500.11937-18615 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:26:38Z |
| publishDate | 2011 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-186152017-09-13T13:47:28Z 3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors Arooj, Mahreen Thangapandian, S. John, S. Hwang, S. Park, J. Lee, K. Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed. A highly correlating (r = 0.942) pharmacophore model (Hypo1) with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated. After successfully validating "Hypo1", it is further applied in database screening. Hit compounds are subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits. Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC 50) data thus successfully validating "Hypo1" by DFT method. Therefore, this research exertion can be helpful in the development of new potent hits for chymase. In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors. © 2011 by the authors; licensee MDPI, Basel, Switzerland. 2011 Journal Article http://hdl.handle.net/20.500.11937/18615 10.3390/ijms12129236 unknown |
| spellingShingle | Arooj, Mahreen Thangapandian, S. John, S. Hwang, S. Park, J. Lee, K. 3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors |
| title | 3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors |
| title_full | 3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors |
| title_fullStr | 3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors |
| title_full_unstemmed | 3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors |
| title_short | 3D QSAR pharmacophore modeling, in silico screening, and density functional theory (DFT) approaches for identification of human chymase inhibitors |
| title_sort | 3d qsar pharmacophore modeling, in silico screening, and density functional theory (dft) approaches for identification of human chymase inhibitors |
| url | http://hdl.handle.net/20.500.11937/18615 |