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Information × Registration Number 0220U104462, 0120U104732 , R & D reports Title Development and in vivo testing of inhibitors of protein kinase C beta, a key enzyme of neutrophilic extracellular traps (NETs) induction, for prevention of acute respiratory distress syndrome (ARDS) popup.stage_title Head Yarmoliuk Serhii M., Доктор хімічних наук Registration Date 18-12-2020 Organization Institute of Molecular Biology and Genetics of NAS of Ukraine popup.description2  As a result of the work, ligand-oriented pharmacophore models of human protein kinase PKCB inhibitors were developed. 4120 compounds were selected according to the results of pharmacophore screening against them. Molecular docking was performed into the ATP-binding site of PKCB and 351 compounds were selected, which were crossed with the results of pharmacophore modeling. Finally, the top 20 compounds were selected for biochemical testing by both screenings. They were tested for their ability to inhibit the activity of neutrophil traps compared to PMA-activated samples. The efficiency of three small molecule compounds is revealed. Acute respiratory distress syndrome (ARDS) in SHR rats was also simulated by intratracheal spraying of PolyI: C synthetic RNA followed by hyperventilation on a Flexivent device. The severity of the course of acute respiratory syndrome was assessed by various markers: functional, macroscopic, biochemical, genetic, morphological and fluorometric. Some indicators of lung respiratory function, such as lung distensibility and rigidity, were determined. The number of extracellular neutrophil traps (NETs) in the circulating blood was determined. The amount of extracellular DNA in the bronchopulmonary lavage and plasma of rats was also determined. The level of expression of a number of proinflammatory cytokines (TNFalpha, interleukin 6 and 10) was evaluated. The constructed pharmacophore models can be used by other research groups in Ukraine and the world for pharmacophore screening to search for new classes of PKCB inhibitors. Identified hit compounds can be used as blockers of NETs to prevent the development of ARDS. They can be the basis for further optimization and biological research. Product Description popup.authors Bdzhola Volodymyr G. Kozak Taisiya O. Pashevin Denys O. Polishchuk Valentina O. Protopopov Mykola V. Starosyla Sergiy A. Stroi Dmytro O. popup.nrat_date 2020-12-18 Close