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Theoretical Investigations on Interactions of Arylsulphonyl Indazole Derivatives as Potential Ligands of VEGFR2 Kinase

1
Chair and Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60-780 Poznań, Poland
2
Faculty of Chemical Engineering and Technology, Cracow University of Technology, ul. Warszawska 24, 31-155 Kraków, Poland
3
Maj Institute of Pharmacology, Polish Academy of Sciences, ul. Smętna 12, 31-343 Kraków, Poland
4
Chair and Department of Pharmacology, Faculty of Pharmacy, Poznan University of Medical Sciences, ul. Rokietnicka 5a, 60-806 Poznań, Poland
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4793; https://doi.org/10.3390/ijms21134793
Received: 26 May 2020 / Revised: 28 June 2020 / Accepted: 3 July 2020 / Published: 7 July 2020
(This article belongs to the Section Molecular Pharmacology)
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. View Full-Text
Keywords: azoles; kinases; VEGFR2 kinase; DFT calculations; semi-empirical calculations; docking; PIEDA analysis; molecular dynamics; hydrogen bond azoles; kinases; VEGFR2 kinase; DFT calculations; semi-empirical calculations; docking; PIEDA analysis; molecular dynamics; hydrogen bond
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MDPI and ACS Style

Czaja, K.; Kujawski, J.; Śliwa, P.; Kurczab, R.; Kujawski, R.; Stodolna, A.; Myślińska, A.; Bernard, M.K. Theoretical Investigations on Interactions of Arylsulphonyl Indazole Derivatives as Potential Ligands of VEGFR2 Kinase. Int. J. Mol. Sci. 2020, 21, 4793.

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