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Molecular docking of ZSTK474 derivatives as potential PI3K-delta inhibitory agents

Liudmyla K. Sviatenko, Oksana V. Tereshchenko


The phosphatidylinositol 3-kinase delta (PI3Kd) controls a range of cellular processes. Its overexpression is found in many human tumors. PI3Kd inhibitors are potential anticancer agents and anti-inflammatory agents for treatment of rheumatoid arthritis. Derivatives of ZSTK474, an effective inhibitor of PI3Kd, were screened virtually by computational docking for inhibitory activity towards PI3Kd. Some of modeled compounds showed better docking energies than ZSTK474 indicating that the former could be potent enzyme inhibitors. Additional binding energy was provided by extra ligand-protein interactions. Substituents in morpholine and benzimidazole rings cause increase and decrease of ligand-protein binding, respectively. Energetically favorable ZSTK474 derivatives satisfy Lipinski’s Rule of five which testifies to their druglikeness (absorption, distribution, metabolism and excretion) and possible pharmacological activity.


molecular docking; binding energy; binding site; inhibitors

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