TY - JOUR
T1 - Preparation, Characterization, and Anticancer Activity of a Series of cis-PtCl2 Complexes Linked to Anthraquinone Intercalators
AU - Gibson, Dan
AU - Gean, Keria Fiorella
AU - Ben-Shoshan, Raphael
AU - Katzhendler, Jehoshua
AU - Ramu, Avner
AU - Ringel, Israel
PY - 1991/1/1
Y1 - 1991/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026087006&partnerID=8YFLogxK
U2 - 10.1021/jm00105a063
DO - 10.1021/jm00105a063
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C2 - 1992142
AN - SCOPUS:0026087006
SN - 0022-2623
VL - 34
SP - 414
EP - 420
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 1
ER -