Preparation, Characterization, and Anticancer Activity of a Series of cis-PtCl₂ Complexes Linked to Anthraquinone Intercalators

A new series of complexes of the type cis-PtL₂X₂[where L is a monodentate AQ-Y(CH₂)_nNH₂and L₂is a bidentate AQ-Y(CH₂)_nNH(CH₂)₂NH₂; AQ = anthraquinone, X = Cl, I, Y = NH, O] in which anthraquinone intercalators are tethered to the cis-PtCl₂unit via an (aminoalkyl)amino,(oxyalkyl)amino, or polyethylene glycol (aminoethyl)amino linker chains was prepared and screened in vitro against P388 leukemia. In vivo toxicity studies were carried out on selected complexes. All complexes were characterized by means of elemental analysis, ¹⁹⁵Pt NMR spectroscopy, and FTIR. The 1:1 Pt-intercalator complexes displayed much higher in vitro cytotoxic activities than the 1:2 Pt-intercalator complexes. The dichloride complexes were consistently more active than their diiodide counterparts. Among the 1:1 Pt-intercalator complexes those with the shorter linker chains (n = 2, 3) exhibited the highest cytotoxic activities. Three compounds, [[2-[[2-(anthraquinon-1-ylamino)ethyl]amino]ethyl]amine-N,N′]dichloroplatinum(II), [[2-[[3-(anthraquinon-1-ylamino)propyl]amino]ethyl]amine-N, N′]dichloroplatinum(II), and [[2-[[3-(anthra- quinon-1-yloxy)propyl]amino]ethyl]amine-N, N′]dichloroplatinum(II), were as active in vitro as cisplatin (ED₅₀= 2-4 × 10^-7 M) while on a molar basis their acute in vivo toxicity was significantly lower than that of cisplatin. In vivo screening against P388 leukemia indicated that these complexes have activity comparable to cisplatin.