Synthesis and Antitumor Activity of Pt(II) Complexes of Benzyl‐1,2‐diaminoethane Ligands

Abstract

Twelve new diamine ligands are synthesized and characterized in which a benzyl group and another vicinal substituent or a benzyl group, a 4‐Cl‐benzyl group, and a 4‐MeO‐benzyl group, respectively, and two other geminal substituents are attached to the 1,2‐diaminoethane skeleton. The diamine ligands are transformed into the dichloroplatinum(II) complexes. The chloride ligands of four complexes are replaced by the lactate anion, α‐Cyclodextrin and polyvinylpyrrolidone are used to increase the water solubility of the Pt(II) complexes. The antitumor activity of the Pt(II) complexes is tested towards the P388 leukemia. The compounds with small alkyl substituents show antitumor activities which are much higher than the antitumor activity of cis‐platinum. Compared to the insoluble dichloro complexes, the lactate complexes and the formulations with α‐cyclodextrin and polyvinylpyrrolidone exhibit good water solubility, and no decrease of the antitumor activity is observed.

Synthese und Antitumoraktivität von [1,2-Diamino-1-(p-hydroxy)benzyl]ethan(dichloro)platin(II)-Komplexen<br />Synthesis and Antitumor Activity of [1,2-Diamino-1-(p-hydroxy)benzyl]ethane(dichloro)platinum(II) Complexes

“…Nach einiger Zeit fallen die Komplexe 13 und 14 als gel be Feststoffe aus (Schema 1). Der Ligand 12 ist bei pH 6 wasserunlöslich, so daß auf ein Reaktionsge misch aus Wasser und terf-Butanol [5] zurückge griffen wird, um den Komplex 15 zu erhalten. Die Komplexe 13-15 sind anhand von IR, 'H -N M R und Elementaranalyse charakterisiert.…”

“…D a die schlechte Löslichkeit von Platin(II)-Komplexen au f die Bildung von K olum narstrukturen zurückgeführt wird [4], w ur de die Wasserlöslichkeit durch Substitution des 1,2-Diaminoethangerüstes erhöht (Störung der K olum narstrukturen) [5]. Neben der Substitution am Diaminliganden wurde die Löslichkeit auch durch Einführung von Abgangsgruppen wie Malonat, Oxalat und Hydroxycarboxylat verbessert [6][7][8][9], Die vorliegende Arbeit zeigt, daß auch die Einführung einer hydrophilen /»-Hydroxygruppe am Benzylrest in drei verschiedenen 1,2-Diaminoethanliganden eine gute Wasserlöslichkeit der resultierenden Komplexe [l,2-Diamino-l-(/?-hydroxy)benzyl-l-(methyl, ethyl bzw.…”

$$N$$ N -Polybenzylated alicyclic 1,2-diamines: cytotoxicity and G1 phase arrest in cancer cell line

“…Antitumoral properties of cisplatin [10] and its success in chemotherapy brought about the synthesis of many diammine-platinum complexes with improved properties, such as oxaliplatin and DWA 2114R. Several 1,2-diamine-platinum complexes were prepared and tested for antitumoral activity, making these compounds the most popular examples of 1,2-diamines in medicinal chemistry [11][12][13][14][15][16][17]. Few others "non-metallic" compounds possessing the 1,2-diamino moiety showed anticancer activity, too.…”

Synthesis of 5,6-O-Cyclohexylidene-1-amino-3-azahexane and Its Co(II), Ni(II), Cu(II) Complexes

“…Complexes formed by the reactions of diamines with transition metals have a wide range of applications [1][2][3][4][5]. For instance, they are used for the determination of mercury in natural waters [6], production of colored thermoplastic resins and formation of crosslinked structures for epoxy resin [7,8], determination of selenium with instrumental methods [9], prevention of corrosion [10,11], pressure sensitive colored imagine technologies [12], powdered hair dyes [13], copolymerizations via cation exchange [14], and in some antiallergic components in medicine [9].…”