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CHROMONE-3-ALDEHYDE DERIVATIVES - SIRTUIN - 2 INHIBITORS IN THE CORRECTION OF MUSCULAR DYSFUNCTION. IN SILICO & IN VIVO STUDY

DOI: https://doi.org/10.29296/25877313-2019-02-07
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Issue: 
2
Year: 
2019

V.М. Rukovitsyna Post-graduate Student, Department of Organic Chemistry, Pyatigorsk Medical Pharmaceutical Institute  branch of the FSEI HE «Volgograd State Medical University» E.T. Oganesyan Professor, Dr.Sc. (Pharm.), Head of the Department of Organic Chemistry, Pyatigorsk Medical Pharmaceutical Institute  branch of the FSEI HE «Volgograd State Medical University» D.I. Pozdnyakov Ph.D. (Med.), Senior Lecturer, Department of Pharmacology, Course of Clinical Pharmacology, Pyatigorsk Medical Pharmaceutical Institute  branch of the FSEI HE «Volgograd State Medical University» E-mail: pozdniackow.dmitry@yandex.ru A.V. Voronkov Dr.Sc. (Med.), Associate Professor, Head of the Department of Pharmacology with the Course of Clinical Pharmacology, Pyatigorsk Medical Pharmaceutical Institute  branch of the FSEI HE «Volgograd State Medical University» O.F. Veselova Ph.D. (Med.), Associate Professor, Head of the Department of Pharmacology and Pharmaceutical Consulting, Professor V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University of Ministry of Health of the Russian Federation E.A. Оlokhova Assistant, Department of Pharmacology and Pharmaceutical Consulting, Professor V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University of Ministry of Health of the Russian Federation A.S. Cherapkin Student, Pyatigorsk Medical Pharmaceutical Institute  branch of the FSEI HE «Volgograd State Medical University»

Aim of the study. Evaluate the ability of derived chromone-3-aldehyde to inhibit the function of sirtuin 2 in conditions of muscle dysfunction. Materials and methods. In this work uses an integrated approach by in silico and in vivo tests. In silico prognosis of pharmacological activity (possibility of correction of muscle dysfunction) of new derivatives of chromone-3-aldehyde was carried out using the PASS program. The probabilistic evaluation of the interaction of the studied substances with sirtuin 2 was performed by molecular docking. In vivo study was performed on male Wistar rats, who were modeled muscle dysfunction by electromyostimulation method. The test-objects were administrated per os, prophylactically for 7 days. Af-ter that, biological material (muscle tissue) was taken, in which the level of sirtuin 2 was determined by the ELISA method. Result. As a result, in silico studies found that in a number of studied objects the most pronounced sirtuin 2 inhibitory properties has acyl-substituted derivative of chromone-3-aldehyde, the energy of interaction of the substance with the target molecule was -129,718 kcal/mol. The molecular modeling data were confirmed by the results of in vivo study in which the course application of the acyl-substituted chromone-3-aldehyde derivative re-duced the activity of sirtuin 2 by 218.8% (p

Keywords: 
molecular docking
muscle dysfunction
sirtuins
chromone derivatives

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