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Synthesis of nanostructuric calixarene effectors of biochemical processes and prospectives of their bio-medical applications
Rodik Roman V.
Кандидат хімічних наук
Institute of Organic Chemistry
Зав. лабораторії
Application bio-inspirited nanostructured molecules with supramolecular properties is considered as a new step in the development of creation various effectors of biochemical processes modern methods, opening up new perspectives in the treatment of diseases (eg, gene therapy) and medical diagnostics. These molecules include calixarenes – nanoscale compounds cup-shaped architecture that are easy available by precision cyclocondensation of para-substituted phenol and formaldehyde. Due to the original molecular architecture calixarenes are able to selective recognition, binding and separation of molecules including biomolecules and biopolymers diverse nature. Owing to ability to mimic the function of natural ionophores, enzymes and antibodies, calixarenes are widely used in biomedical research. Synthesized by R.V. Rodik sulfonylamidinocalixarenes selectively inhibit enzymatic activity of transport Ca2+,Mg2+,ATPase (Mg2+,ATP-dependent calcium pump, І0,5=20,2±0,5 µM) of myometrium cells plasma membrane and practically didn’t influenced to activity of other ATP-hydrolase. This result is fundamental, because the low-selective inhibitors of the above-mentioned calcium pump are unknown. Calix[4]arene-aminophosphonic acid selectively inhibit the transport activity of Na+, K+-ATPase plasma membrane (І0,5 = 54±4 nM). The molecular model of complexation between myosin subfragment-1 and this calixarenes was built up by methods of docking and molecular dynamics. Developed by R.V. Rodik methods of calixarenes functionalization allow to quick and high-yields synthesis of macrocycle decorated with amide, amidine, urea, imine and other bio-phoric groups. He proposed methods for synthesis of calixarenes modified by highly-reacted imidoylchloride and isocyanate groups that were successfully used for the obtaining of calixarenes with sensor, metal-coordinating and receptor groups. Results of cytological studies of obtained by R.V. Rodik cationic amphiphilic calixarenes show their binding to DNA and its transport into cells with aim to correct genetic defects. Water-soluble calixarenes with methylimidazol and ethylendiamine groups exhibit significant antibacterial effect, higher than similar quaternary ammonium salts. In vivo studies showed that the synthesized by R.V. Rodik carbamidocalixarenes show significant hypoglycemic effect. The results may be useful in developing of new drugs against diabetes mellitus type II. Scientific results of R.V. Rodik published at 2 reviews and 37 articles in leading international and national journals and 7 patents of Ukraine. There is about 200 references to Rodik’s papers according to scientometrics Scopus database, the index Hirsch is 7.
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Інститут програмних систем НАН України
, 2023