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Information × Registration Number 0222U001229, 0121U111200 , R & D reports Title Molecular design, creation, in vitro and in vivo screening of nanocomplexes of natural alkaloids with C60 fullerene to increase the effectiveness of metastatic cancer therapy popup.stage_title Head Prylutskyi Yurii I., Доктор фізико-математичних наук Registration Date 25-01-2022 Organization Taras Shevchenko National University of Kyiv popup.description2 The object of research is the interaction of C60 fullerene with alkaloid molecules. The purpose of the work is to determine the antitumor activity of the C60-alkaloid complex. Research methods: UV-Vis and mass spectroscopy, dynamic light scattering, high performance liquid chromatography, molecular dynamics, docking. Using the original ultrasonic technology and spectroscopic methods, water-soluble C60-alkaloid complexes (berberine (BBR), piperlongumine (PL) and homoharringtonine (HHT)) in different molar ratios of components were prepared and characterized. Using the molecular dynamics (MD) simulation, it has been shown that C60 fullerene nanocomplexes with 5 non-covalently bound BBR or PL molecules are the most stable in the aqueous medium. The dynamic light scattering measurements revealed the presence of large particles in the studied aqueous dispersion of C60-HHT (797 nm in diameter). MD data showed that HHT molecules are adsorbed mostly not on a single C60 molecule, but on its nanoclusters due to steric and stacking interactions between the aromatic parts of these molecules. Using a high performance liquid chromatography, it was found that 2:1 C60-BBR, 2:1 C60-PL and 2:1 C60-HHT complexes release BBR, PL and HHT molecules, correspondingly, faster in an acidic (tumor site simulation) than in a physiological media. Molecular docking results indicate that the C60 molecule loaded with BBR binds to the P-gp plasma membrane transporter protein due to Van der Waals forces and induces its conformational changes. The results of molecular docking indicate the potential binding of C60 fullerene to the HDAC1 enzyme, although within the MD such complex is unstable. At the same time, the PL-HDAC1 and HHT-HDAC1 complexes proved to be the most stable. Therefore, it can be reliably stated that C60 fullerenes (both single and their nanoclusters) loaded with PL or HHT molecules are able to inhibit the functional activity of the HDAC1 enzyme, considered as a molecular target.  Product Description popup.authors Gurmach Vasylʹ V. Prylutska Svitlana V. Franskevych Daria V. popup.nrat_date 2022-03-09 Close