3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma
Background: Quinazolines are an important class of benzopyrimidine heterocyclic compounds with a promising antitumor activity that can be used for the design and development of osteosarcoma target compounds.Objective: To predict the compound activity of quinazoline compounds by constructing 2D- and...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1124895/full |
| _version_ | 1797901017591840768 |
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| author | Zheng Lian Chenglin Sang Nianhu Li Honglin Zhai Wenzhe Bai |
| author_facet | Zheng Lian Chenglin Sang Nianhu Li Honglin Zhai Wenzhe Bai |
| author_sort | Zheng Lian |
| collection | DOAJ |
| description | Background: Quinazolines are an important class of benzopyrimidine heterocyclic compounds with a promising antitumor activity that can be used for the design and development of osteosarcoma target compounds.Objective: To predict the compound activity of quinazoline compounds by constructing 2D- and 3D-QSAR models, and to design new compounds according to the main influencing factors of compound activity in the two models.Methods: First, heuristic method and GEP (gene expression programming) algorithm were used to construct linear and non-linear 2D-QSAR models. Then a 3D-QSAR model was constructed using CoMSIA method in SYBYL software package. Finally, new compounds were designed according to molecular descriptors of 2D-QSAR model and contour maps of 3D-QSAR model. Several compounds with optimal activity were used for docking experiments with osteosarcoma related targets (FGFR4).Results: The non-linear model constructed by GEP algorithm was more stable and predictive than the linear model constructed by heuristic method. A 3D-QSAR model with high Q2 (0.63) and R2 (0.987) values and low error values (0.05) was obtained in this study. The success of the model fully passed the external validation formula, proving that the model is very stable and has strong predictive power. 200 quinazoline derivatives were designed according to molecular descriptors and contour maps, and docking experiments were carried out for the most active compounds. Compound 19g.10 has the best compound activity with good target binding capability.Conclusion: To sum up, the two novel QSAR models constructed were very reliable. The combination of descriptors in 2D-QSAR with COMSIA contour maps provides new design ideas for future compound design in osteosarcoma. |
| first_indexed | 2024-04-10T08:54:12Z |
| format | Article |
| id | doaj.art-25d0fd748dd44c7fb4b4aef215088c93 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-10T08:54:12Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-25d0fd748dd44c7fb4b4aef215088c932023-02-21T17:01:55ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-02-011410.3389/fphar.2023.112489511248953D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcomaZheng Lian0Chenglin Sang1Nianhu Li2Honglin Zhai3Wenzhe Bai4School of Clinical Medicine, Weifang Medical University, Weifang, ChinaDepartment of Orthopedics, The 960th Hospital of the Chinese People’s Liberation Army, Jinan, ChinaThe First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Orthopedics, The 960th Hospital of the Chinese People’s Liberation Army, Jinan, ChinaThe First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan, ChinaBackground: Quinazolines are an important class of benzopyrimidine heterocyclic compounds with a promising antitumor activity that can be used for the design and development of osteosarcoma target compounds.Objective: To predict the compound activity of quinazoline compounds by constructing 2D- and 3D-QSAR models, and to design new compounds according to the main influencing factors of compound activity in the two models.Methods: First, heuristic method and GEP (gene expression programming) algorithm were used to construct linear and non-linear 2D-QSAR models. Then a 3D-QSAR model was constructed using CoMSIA method in SYBYL software package. Finally, new compounds were designed according to molecular descriptors of 2D-QSAR model and contour maps of 3D-QSAR model. Several compounds with optimal activity were used for docking experiments with osteosarcoma related targets (FGFR4).Results: The non-linear model constructed by GEP algorithm was more stable and predictive than the linear model constructed by heuristic method. A 3D-QSAR model with high Q2 (0.63) and R2 (0.987) values and low error values (0.05) was obtained in this study. The success of the model fully passed the external validation formula, proving that the model is very stable and has strong predictive power. 200 quinazoline derivatives were designed according to molecular descriptors and contour maps, and docking experiments were carried out for the most active compounds. Compound 19g.10 has the best compound activity with good target binding capability.Conclusion: To sum up, the two novel QSAR models constructed were very reliable. The combination of descriptors in 2D-QSAR with COMSIA contour maps provides new design ideas for future compound design in osteosarcoma.https://www.frontiersin.org/articles/10.3389/fphar.2023.1124895/fullquinazolinesstructure-activity relationshiposteosarcomaTargeted drugssmall molecule docking |
| spellingShingle | Zheng Lian Chenglin Sang Nianhu Li Honglin Zhai Wenzhe Bai 3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma Frontiers in Pharmacology quinazolines structure-activity relationship osteosarcoma Targeted drugs small molecule docking |
| title | 3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma |
| title_full | 3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma |
| title_fullStr | 3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma |
| title_full_unstemmed | 3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma |
| title_short | 3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma |
| title_sort | 3d 2d qsar study and docking of novel quinazolines as potential target drugs for osteosarcoma |
| topic | quinazolines structure-activity relationship osteosarcoma Targeted drugs small molecule docking |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1124895/full |
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