ABSTRACT
Purpose: One of the promising chemical groups for the development of new antihypertensive medicines, the action of which is associated with the inhibition of phosphodiesterase III (PDE3) activity, are phosphorylated oxazole derivatives (OVPs). This study aimed to prove experimentally the presence of the OVPs antihypertensive effect associated with decreasing of PDE activity and to justify its molecular mechanism. Methods: An experimental study of the effect of OVPs on phosphodiesterase activity was performed on Wistar rats. Determination of PDE activity was performed by fluorimetric method using umbelliferon in blood serum and organs. The docking method was used to investigate the potential molecular mechanisms of the antihypertensive action of OVPs with PDE3. Results: The introduction of OVP-1 50 mg/kg, as a leader compound, led to the restoration of PDE activity in the aorta, heart and serum of rats with hypertension to the values observed in the intact group. This may indicate the possibility of the development of vasodilating action of OVPs by the influence of the latter on the increase in cGMP synthesis due to inhibition of PDE activity. The calculated results of molecular docking of ligands OVPs to the active site of PDE3 showed that all test compounds have a common type of complexation due to phosphonate groups, piperidine rings, side and terminal phenyl and methylphenyl groups. Conclusion: The analysis of the obtained results both in vivo and in silico showed that phosphorylated oxazole derivatives represent a new platform for further studies as phosphodiesterase III inhibitors with antihypertensive activity.
ABSTRACT
The article presents the results of the investigation of the effect of biomass powder of the fungus Ganoderma lucidum on T-cell-mediated immunity in normal and immunosuppressed mice CBA/Ca. Delayed-type hypersensitivity assay was used. Experimental immunodeficiency was established with intraperitoneal injection of the immunosuppressant cyclophosphamide at a single dose of 150 mg/kg on the first day of the experiment. Results of the study show that the administration of biomass powder of Ganoderma lucidum in a dose of 0.5 mg/kg orally for 10 days increases the delayed-type hypersensitivity response in normal mice CBA/Ca. Administration of 0.5 mg/kg of biomass powder of the fungus Ganoderma lucidum for 10 days blocked the development of the T-cell-mediated immunosuppression, induced by administration of cyclophosphamide and restored the delayed-type hypersensitivity response in immunosuppressed mice. Key words: fungus Ganoderma lucidum cyclophosphamide immunodeficiency T-cell-mediated immunity delayed-type hypersensitivity.
