Theoretical investigations on interactions of arylsulphonyl indazole derivatives as potential ligands of VEGFR2 kinase
Authors:
- Kornelia Czaja,
- Jacek Kujawski,
- Paweł Śliwa,
- Rafał Kurczab,
- Radosław Kujawski,
- Anna Stodolna,
- Agnieszka Myślińska,
- Marek K. Bernard
Abstract
Vascular endothelial growth factor receptor 2 (VEGFR2) is a key receptor in the angiogenesis process. The VEGFR2 expression is upregulated in many cancers so this receptor is an important target for anticancer agents. In the present paper, we analyse interactions of several dimeric indazoles, previously investigated for anticancer activity, with the amino acids present in the VEGFR2 binding pocket. Using the docking method and MD simulations as well as theoretical computations (SAPT0, PIEDA, semi-empirical PM7), we confirmed that these azoles can efficiently bind into the kinase pocket and their poses can be stabilised by the formation of hydrogen bonds, π–π stacking, π–cation, and hybrid interactions with some amino acids of the kinase cavity like Ala866, Lys868, Glu885, Thr916, Glu917, and Phe918.
- Record ID
- CUT523827e05a894d4ba0bde7610b94dda7
- Publication categories
- ;
- Author
- Journal series
- International Journal of Molecular Sciences, ISSN 1661-6596, e-ISSN 1422-0067, Biweekly
- Issue year
- 2020
- Vol
- 21
- No
- 13
- Pages
- 1-24
- Article number
- 4793
- Other elements of collation
- rys.; schem.; tab.; wykr.; Bibliografia (na s.) - 21-24; Bibliografia (liczba pozycji) - 60; Oznaczenie streszczenia - Abstr.; Numeracja w czasopiśmie - Vol. 21, Iss. 13
- Substantive notes
- Section: Molecular Pharmacology
- Art. zawiera Supplementary Material
- Keywords in English
- azoles, kinases, VEGFR2 kinase, DFT calculations, semi-empirical calculations, docking, PIEDA analysis, molecular dynamics, hydrogen bond
- DOI
- DOI:10.3390/ijms21134793 Opening in a new tab
- URL
- https://www.mdpi.com/1422-0067/21/13/4793 Opening in a new tab
- Language
- eng (en) English
- License
- Score (nominal)
- 140
- Additional fields
- Indeksowana w: Web of Science, Scopus
- Uniform Resource Identifier
- https://cris.pk.edu.pl/info/article/CUT523827e05a894d4ba0bde7610b94dda7/
- URN
urn:pkr-prod:CUT523827e05a894d4ba0bde7610b94dda7
* presented citation count is obtained through Internet information analysis, and it is close to the number calculated by the Publish or PerishOpening in a new tab system.