Theoretical Investigations on Interactions of Arylsulphonyl Indazole Derivatives as Potential Ligands of VEGFR2 Kinase
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, previo...
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| Veröffentlicht in: | International journal of molecular sciences 2020-07, Vol.21 (13), p.4793 |
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| creator | Czaja, Kornelia Kujawski, Jacek Śliwa, Paweł Kurczab, Rafał Kujawski, Radosław Stodolna, Anna Myślińska, Agnieszka Bernard, Marek K |
| description | 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. |
| doi_str_mv | 10.3390/ijms21134793 |
| format | Article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21134793</identifier><identifier>PMID: 32645858</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Amino acids ; Amino Acids - metabolism ; Angiogenesis ; Antineoplastic Agents - metabolism ; Antitumor activity ; Azoles ; Azoles - metabolism ; Binding Sites - physiology ; Cancer ; Clinical trials ; Computer simulation ; Enzymes ; FDA approval ; Growth factors ; Heterocyclic compounds ; Humans ; Hydrogen Bonding ; Hydrogen bonds ; Indazoles - metabolism ; Kinases ; Leukemia ; Ligands ; Lymphoma ; Metastasis ; Molecular Docking Simulation - methods ; Molecular Dynamics Simulation ; Nitrogen ; Protein Binding - physiology ; Proteins ; Tumors ; Vascular endothelial growth factor ; Vascular endothelial growth factor receptor 2 ; Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><ispartof>International journal of molecular sciences, 2020-07, Vol.21 (13), p.4793</ispartof><rights>2020. 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32645858</pmid><doi>10.3390/ijms21134793</doi><orcidid>https://orcid.org/0000-0001-6279-4887</orcidid><orcidid>https://orcid.org/0000-0001-9662-8481</orcidid><orcidid>https://orcid.org/0000-0002-9555-3905</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Amino acids Amino Acids - metabolism Angiogenesis Antineoplastic Agents - metabolism Antitumor activity Azoles Azoles - metabolism Binding Sites - physiology Cancer Clinical trials Computer simulation Enzymes FDA approval Growth factors Heterocyclic compounds Humans Hydrogen Bonding Hydrogen bonds Indazoles - metabolism Kinases Leukemia Ligands Lymphoma Metastasis Molecular Docking Simulation - methods Molecular Dynamics Simulation Nitrogen Protein Binding - physiology Proteins Tumors Vascular endothelial growth factor Vascular endothelial growth factor receptor 2 Vascular Endothelial Growth Factor Receptor-2 - metabolism |
| title | Theoretical Investigations on Interactions of Arylsulphonyl Indazole Derivatives as Potential Ligands of VEGFR2 Kinase |
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