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

Dan Gibson*, Keria Fiorella Gean, Raphael Ben-Shoshan, Jehoshua Katzhendler, Avner Ramu, Israel Ringel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)414-420
Number of pages7
JournalJournal of Medicinal Chemistry
Volume34
Issue number1
DOIs
StatePublished - 1 Jan 1991

Fingerprint

Dive into the research topics of 'Preparation, Characterization, and Anticancer Activity of a Series of cis-PtCl2 Complexes Linked to Anthraquinone Intercalators'. Together they form a unique fingerprint.

Cite this