СИНТЕЗ НОВЫХ БИОЛОГИЧЕСКИ АКТИВНЫХ ПОЛИМЕРНЫХ БИОКОНЪЮГАТОВ НА ОСНОВЕ ЛУПАНОВЫХ АЛЛИЛАМИДОВ

Abstract

The work is devoted to the synthesis of new copolymers based on allylamides of betulonic and 2 hydroximinobetulonic acids and study of their cytotoxic activity. Allylamides of betulonic and 2 hydroximinobetulonic acids were prepared by the reaction of corresponding acids with allylamine in the presence of oxalyl chloride and triethylamine. It was established that the allylamides obtained do not homopolymerize, but copolymerize with low rates with acrylonitrile and N-vinylpyrrolidone in the presence of radical initiators The investigations of radical copolymerization of allylamides with acrylonitrile and N-vinyl­pyrrolidone showed that the resulting copolymers have a statistical distribution of the comonomer units in the macromolecule, wherein in the entire range of monomer concentrations the copolymers are enriched by the vinyl monomer units. The copolymerization rates are considerably reduced by increasing the content of allylamides in the initial monomer mixture in all copolymerization systems, the copolymerization rate of allylamide with acrylonitrile is higher than with N-vinylpyrrolidone. At the copolymerization in bulk with enhancing degree of conversion there is a gel-effect, which is associated with an increasing of the viscosity in the absence of solvent; at the copolymerization in solution gel-effect is absent. The structure of the copolymers obtained was determined by 1 H NMR spectroscopy. It was established that the products obtained are a mixture of copolymers of allyl amides and oligomers thereof. In the spectra of the reaction products a number of additions of the vinyl monomer with the participating of double bond of isopropylidene group is also observed. The copolymers obtained have a cytotoxic activity: the copolymer of allylamide of betulonic acid with N-vinylpyrrolidone exhibits 4-fold higher activity against MS culture when compared with the initial ally amide and is promising for developing new bioactive polymer bioconjugates.