Pharmacophore modeling, docking and molecular dynamics simulation for identification of novel human protein kinase C beta (PKCβ) inhibitors.

Autor: Starosyla SA; 150 Zabolotnogo St, Kyiv, 03143 Ukraine Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics, NAS of Ukraine.; RECEPTOR.AI, Boston, MA USA., Volynets GP; 150 Zabolotnogo St, Kyiv, 03143 Ukraine Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics, NAS of Ukraine., Protopopov MV; 150 Zabolotnogo St, Kyiv, 03143 Ukraine Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics, NAS of Ukraine., Bdzhola VG; 150 Zabolotnogo St, Kyiv, 03143 Ukraine Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics, NAS of Ukraine., Pashevin DO; Kyiv, 01024 Ukraine Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology., Polishchuk VO; Kyiv, 01024 Ukraine Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology., Kozak TO; Kyiv, 01024 Ukraine Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology., Stroi DO; Kyiv, 01024 Ukraine Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology., Dosenko VE; Kyiv, 01024 Ukraine Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology., Yarmoluk SM; 150 Zabolotnogo St, Kyiv, 03143 Ukraine Department of Medicinal Chemistry, Institute of Molecular Biology and Genetics, NAS of Ukraine.
Jazyk: angličtina
Zdroj: Structural chemistry [Struct Chem] 2023; Vol. 34 (3), pp. 1157-1171. Date of Electronic Publication: 2022 Oct 11.
DOI: 10.1007/s11224-022-02075-y
Abstrakt: Protein kinase Cβ (PKCβ) is considered as an attractive molecular target for the treatment of COVID-19-related acute respiratory distress syndrome (ARDS). Several classes of inhibitors have been already identified. In this article, we developed and validated ligand-based PKCβ pharmacophore models based on the chemical structures of the known inhibitors. The most accurate pharmacophore model, which correctly predicted more than 70% active compounds of test set, included three aromatic pharmacophore features without vectors, one hydrogen bond acceptor pharmacophore feature, one hydrophobic pharmacophore feature and 158 excluded volumes. This pharmacophore model was used for virtual screening of compound collection in order to identify novel potent PKCβ inhibitors. Also, molecular docking of compound collection was performed and 28 compounds which were selected simultaneously by two approaches as top-scored were proposed for further biological research.
Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02075-y.
Competing Interests: Competing interestsThe authors declare no competing interests.
(© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
Databáze: MEDLINE
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