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S. G. Shlykov, A. V. Sylenko, L. G. Babich, S. O. Karakhim, Î. Yu. Chunikhin, O. A. Yesypenko, V. I. Kal’chenko, S. O. Kosterin
«Calix[4]arene Chalcone Amides as Effectors of Mitochondria Membrane Polarization»
473–485 (2020)

PACS numbers: 81.16.Fg, 82.39.Jn, 82.39.Wj, 82.45.Tv, 87.16.D-, 87.16.Tb, 87.50.cj

Calixarenes are supramolecular compounds with a unique three-dimensional structure, the biological activity of which is determined by the chemical groups on the upper or lower rim. As shown in the previous works, using isolated mitochondria and digitonin-permeabilized myometrium cells, the calix[4]arene chalcone amides modulated the levels of both mitochondria-membrane polarization and Ñà\(^{2+}\) concentration in the myometrial mitochondria matrix. As shown, the incubation of the mitochondria with calix[4]arene chalcone amides is accompanied by changes of the average hydrodynamic diameter of mitochondria. The aims of this study are as follow: to investigate the kinetics of the mitochondria diameter changes under the effects of calix[4]arenes with two and four chalcone amide groups; find out whether or not calix[4]arene chalcone amides penetrate into the cell and whether the polarization of the mitochondria membranes undergoes alterations at the incubation of the primary myometrium-cells’ culture with these compounds. Experiments are conducted on two biochemical models: isolated myometrial mitochondria and primary myometrium-cells’ culture. The hydrodynamic diameter of mitochondria is investigated using the dynamic light-scattering method with the use of a laser correlation spectrometer Malvern Instruments ‘ZetaSizer-3’ (United Kingdom). Polarization of mitochondria membranes is investigated using confocal laser scanning microscope LSM 510 META Carl Zeiss. The calix[4]arene chalcone amide C-1070 fluorescence spectrum is studied using the QuantaMasterTM40 spectrofluorimeter (Photon Technology International). As shown: the hydrodynamic diameter of the mitochondria depends on the composition of the incubation medium, and in the presence of ATP, it is smaller than in its absence; the hydrodynamic diameter of the mitochondria increases in time at the incubation of mitochondria with calix[4]arene chalcone amides; calix[4]arene chalcone amides’ effect on the hydrodynamic diameter of the mitochondria increases with an increase in the number of chalcone amide groups in the structure of calix[4]arenes; calix[4]arene chalcone amides’ effect on the hydrodynamic diameter of the mitochondria depends on the composition of the incubation medium, and at the presence of ATP, it is smaller than at its absence. Using calix[4]arene chalcone amide C-1070 (as fluorescent equivalent of C-1011), it is proved that these compounds penetrate the myometrial cells. The modulatory effects of calix[4]arene chalcone amide with two chalcone amide groups on the polarization of the mitochondria membranes is shown using primary myometrium-cell culture and potential-sensitive probe JC-1. Medical statistics indicate that uterine fibroids are widespread pathology. The search for compounds, which can reduce the volume of the tumour, is extremely important. The results allow suggest that calix[4]arene chalcone amides are promising compounds in the further study of their effect on the viability of the undesirable cells due to the launch of apoptosis of mitochondrial pathway.

Keywords: calixarenes, mitochondria membrane potential, myometrium
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