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:
Durch Reaktion des Platinats (I) mit Glycylglycin in Gegenwart Von NaOH (Moi Verhältnis wie l 24: 4) in Wasser bei 25°C und nachfolgende Umsetzung des entn stehenden Anions (II) mit K2[PtCl4] und HCl (Molverhältnis wie l : l : 4) läßt sich das Komplexsalz (III) darstellen.
Bei der Reaktion von K2PtCl4 mit äquimolaren Mengen von Alanylmethionin (HL) in konz. wäßriger Lösung entsteht der Pt(II)‐Komplex (I); dieser Komplex (I) geht unter der Einwirkung äquimolarer KOH‐Mengen reversibel in den Komplex (II) über.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.