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

Kornelia Czaja, Jacek Kujawski, Paweł Śliwa, Rafał Kurczab, Radosław Kujawski, Anna Stodolna, Agnieszka Myślińska, Marek K Bernard

International journal of molecular sciences 2020 Jul 07

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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.

Citation

Kornelia Czaja, Jacek Kujawski, Paweł Śliwa, Rafał Kurczab, Radosław Kujawski, Anna Stodolna, Agnieszka Myślińska, Marek K Bernard. Theoretical Investigations on Interactions of Arylsulphonyl Indazole Derivatives as Potential Ligands of VEGFR2 Kinase. International journal of molecular sciences. 2020 Jul 07;21(13)