Quantitative Structure-Activity Relationship and Molecular Docking of Artemisinin Derivatives to Vascular Endothelial Growth Factor Receptor 1
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Mohamed EM Saeed
- Onnf Kadioglu
- Ean-Jeong Seo
- Henry Johannes Greten
- Ruth Brenk
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000352731600009&DestLinkType=FullRecord&DestApp=WOS_CPL
- eISSN
- 1791-7530
- Externe Identifier
- Clarivate Analytics Document Solution ID: CF7JF
- PubMed Identifier: 25862844
- ISSN
- 0250-7005
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- ANTICANCER RESEARCH
- Schlüsselwörter
- Angiogenesis
- Artemisia annua
- artemisinin
- cancer
- molecu lar docking
- quantitative structure-activity relationship calcula tions
- QSAR
- vascular endothelial growth factor receptor
- Paginierung
- 1929 - 1934
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- Quantitative Structure-Activity Relationship and Molecular Docking of Artemisinin Derivatives to Vascular Endothelial Growth Factor Receptor 1
- Sub types
- Article
- Ausgabe der Zeitschrift
- 35
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <h4>Background/aim</h4>The antimalarial drug artemisinin has been shown to exert anticancer activity through anti-angiogenic effects. For further drug development, it may be useful to have derivatives with improved anti-angiogenic properties.<h4>Material and methods</h4>We performed molecular docking of 52 artemisinin derivatives to vascular endothelial growth factor receptors (VEGFR1, VEGFR2), and VEGFA ligand using Autodock4 and AutodockTools-1.5.7.rc1 using the Lamarckian genetic algorithm. Quantitative structure-activity relationship (QSAR) analyses of the compounds prepared by Corina Molecular Networks were performed using the Molecular Operating Environment MOE 2012.10.<h4>Results</h4>A statistically significant inverse relationship was obtained between in silico binding energies to VEGFR1 and anti-angiogenic activity in vivo of a test-set of artemisinin derivatives (R=-0.843; p=0.035). This served as a control experiment to validate molecular docking predicting anti-angiogenc effects. Furthermore, 52 artemisinin derivatives were docked to VEGFR1 and in selected examples also to VEGFR2 and VEGFA. Higher binding affinities were calculated for receptors than for the ligand. The best binding affinities to VEGFR1 were found for an artemisinin dimer, 10-dihydroartemisinyl-2-propylpentanoate, and dihydroartemisinin α-hemisuccinate sodium salt. QSAR analyses revealed significant relationships between VEGFR1 binding energies and defined molecular descriptors of 35 artemisinins assigned to the training set (R=0.0848, p<0.0001) and 17 derivatives assigned to the test set (R=0.761, p<0.001).<h4>Conclusion</h4>Molecular docking and QSAR calculations can be used to identify novel artemisinin derivatives with anti-angiogenic effects.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
- Autoren
- Mohamed EM Saeed
- Onat Kadioglu
- Ean-Jeong Seo
- Henry Johannes Greten
- Ruth Brenk
- Thomas Efferth
- eISSN
- 1791-7530
- Externe Identifier
- PubMed Identifier: 25862844
- Open access
- false
- ISSN
- 0250-7005
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Anticancer research
- Schlüsselwörter
- Humans
- Artemisinins
- Vascular Endothelial Growth Factor Receptor-1
- Vascular Endothelial Growth Factor Receptor-2
- Vascular Endothelial Growth Factor A
- Ligands
- Binding Sites
- Molecular Structure
- Quantitative Structure-Activity Relationship
- Computer Simulation
- Molecular Docking Simulation
- Sprache
- eng
- Medium
- Paginierung
- 1929 - 1934
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- Quantitative structure-activity relationship and molecular docking of artemisinin derivatives to vascular endothelial growth factor receptor 1.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 35
Data source: Europe PubMed Central
- Abstract
- BACKGROUND/AIM: The antimalarial drug artemisinin has been shown to exert anticancer activity through anti-angiogenic effects. For further drug development, it may be useful to have derivatives with improved anti-angiogenic properties. MATERIAL AND METHODS: We performed molecular docking of 52 artemisinin derivatives to vascular endothelial growth factor receptors (VEGFR1, VEGFR2), and VEGFA ligand using Autodock4 and AutodockTools-1.5.7.rc1 using the Lamarckian genetic algorithm. Quantitative structure-activity relationship (QSAR) analyses of the compounds prepared by Corina Molecular Networks were performed using the Molecular Operating Environment MOE 2012.10. RESULTS: A statistically significant inverse relationship was obtained between in silico binding energies to VEGFR1 and anti-angiogenic activity in vivo of a test-set of artemisinin derivatives (R=-0.843; p=0.035). This served as a control experiment to validate molecular docking predicting anti-angiogenc effects. Furthermore, 52 artemisinin derivatives were docked to VEGFR1 and in selected examples also to VEGFR2 and VEGFA. Higher binding affinities were calculated for receptors than for the ligand. The best binding affinities to VEGFR1 were found for an artemisinin dimer, 10-dihydroartemisinyl-2-propylpentanoate, and dihydroartemisinin α-hemisuccinate sodium salt. QSAR analyses revealed significant relationships between VEGFR1 binding energies and defined molecular descriptors of 35 artemisinins assigned to the training set (R=0.0848, p<0.0001) and 17 derivatives assigned to the test set (R=0.761, p<0.001). CONCLUSION: Molecular docking and QSAR calculations can be used to identify novel artemisinin derivatives with anti-angiogenic effects.
- Autoren
- Mohamed EM Saeed
- Onat Kadioglu
- Ean-Jeong Seo
- Henry Johannes Greten
- Ruth Brenk
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/25862844
- eISSN
- 1791-7530
- Ausgabe der Veröffentlichung
- 4
- Zeitschrift
- Anticancer Res
- Schlüsselwörter
- Angiogenesis
- Artemisia annua
- QSAR
- artemisinin
- cancer
- molecular docking
- quantitative structure-activity relationship calculations
- vascular endothelial growth factor receptor
- Artemisinins
- Binding Sites
- Computer Simulation
- Humans
- Ligands
- Molecular Docking Simulation
- Molecular Structure
- Quantitative Structure-Activity Relationship
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factor Receptor-1
- Vascular Endothelial Growth Factor Receptor-2
- Sprache
- eng
- Country
- Greece
- Paginierung
- 1929 - 1934
- PII
- 35/4/1929
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2015
- Titel
- Quantitative structure-activity relationship and molecular docking of artemisinin derivatives to vascular endothelial growth factor receptor 1.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 35
Data source: PubMed
- Beziehungen:
- Property of