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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990820/ https://www.ncbi.nlm.nih.gov/pubmed/36895941 http://dx.doi.org/10.3389/fphar.2023.1124895 |
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author | Lian, Zheng Sang, Chenglin Li, Nianhu Zhai, Honglin Bai, Wenzhe |
author_facet | Lian, Zheng Sang, Chenglin Li, Nianhu Zhai, Honglin Bai, Wenzhe |
author_sort | Lian, Zheng |
collection | PubMed |
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 Q(2) (0.63) and R (2) (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. |
format | Online Article Text |
id | pubmed-9990820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99908202023-03-08 3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma Lian, Zheng Sang, Chenglin Li, Nianhu Zhai, Honglin Bai, Wenzhe Front Pharmacol Pharmacology 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 Q(2) (0.63) and R (2) (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. Frontiers Media S.A. 2023-02-21 /pmc/articles/PMC9990820/ /pubmed/36895941 http://dx.doi.org/10.3389/fphar.2023.1124895 Text en Copyright © 2023 Lian, Sang, Li, Zhai and Bai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Lian, Zheng Sang, Chenglin Li, Nianhu Zhai, Honglin Bai, Wenzhe 3D,2D-QSAR study and docking of novel quinazolines as potential target drugs for osteosarcoma |
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 | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990820/ https://www.ncbi.nlm.nih.gov/pubmed/36895941 http://dx.doi.org/10.3389/fphar.2023.1124895 |
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