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Effect of the Diamine Nonleaving Group in Platinum−Acridinylthiourea Conjugates on DNA Damage and Cytotoxicity

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journal contribution
posted on 03.05.2007, 00:00 by Rajsekhar Guddneppanavar, Jayati Roy Choudhury, Alexander R. Kheradi, Bartlett D. Steen, Gilda Saluta, Gregory L. Kucera, Cynthia S. Day, Ulrich Bierbach
The following complexes of type [PtCl(R)(ACRAMTU)](NO3)2 (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea)), derived from prototype 1 (with R = ethane-1,2-diamine), were synthesized:  2 (with R = (1R,2R)-1,2-diaminocyclohexane), 3 (with R = propane-1,3-diamine), 4 (with R = N,N1,N,N2-tetramethylethane-1,2-diamine), and 5 (with R = 2,2‘-bipyridine). The DNA sequence specificity of the conjugates and their antiproliferative potential in HL-60 and H460 cells were investigated. Conjugate 3 showed the strongest non-cisplatin-type DNA damage in polymerase stop assays and superior cell kill efficacy in H460 lung cancer (IC50 = 70 nM).