At present, some oncological disorders are commonly treated by cis-dichlorodiammineplatinum (DDP). Unfortunately, DDP and its analogs with other amines are high-toxicity poorly soluble substances having a rather narrow interval of therapeutic dosage. Therefore, it is still an important task to search for new, well-soluble platinum complexes possessing lower toxicity and no cross-resistance with respect to DDP.A promising direction of this search is the synthesis of platinum compounds containing natural cell components in the inner coordination sphere, including amino acids, peptides, and nucleic acid bases, as well as their derivatives and / or antimetabolites.As is known, an increase in the number of electron-donor nitrogen atoms surrounding platinum, which can be achieved by incorporating nucleic acid bases or nucleosides into the inner sphere of the diamine complex, leads to the formation of low-toxicity well-soluble compounds possessing high antitumor activity [1]. Previously reported compounds of this type belonged to the cationic complexes of platinum [1]. However, we may expect that neutral complexes are more promising objects, since the absence of charge on their inner spheres would facilitate penetration of these compounds through the cell membranes.The purpose of this work was to synthesize and characterize with respect to cytotoxic activity a series of new platinum complexes of the tri-and tetraamine types, with the inner spheres containing NH 3 or ethylenediamine (En) molecules and a modified nucleoside-the antitumor agent ftorafur (HE) [2].
HLIntroducing En (rather than two NH3 molecules) into the inner sphere must increase stability of the complex in aqueous solutions. Indeed, the bidentate En forming a five-member cycle excludes the possibility of eis -trans isomerization in this compound.The platinum complexes (I -III) were synthesized by the following schemes:
Morphological and proliferative characteristics of cultured Vero and MDCK cells were compared after growth in nutrient media of the basis of enzymatic hydrolysates of rice flour proteins and soybean flour proteins or control media (DMEM and Axcevir-MDCK). These media had a strong stimulatory effect on the growth of cultured Vero cells (addition of 3% fetal bovine serum, Gibco), but did not modulate the morphology of this culture. Culturing of MDCK cells in nutrient media on the basis of enzymatic hydrolysates of rice and soybean flour proteins with low content of fetal bovine serum (2%, Gibco) was accompanied by insignificant changes in the index of proliferation and morphological characteristics of cultured cells.
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