Design, synthesis, and biological activity of a novel non-cisplatin-type platinum-acridine pharmacophore. |
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| Authors: | E T Martins H Baruah J Kramarczyk G Saluta C S Day G L Kucera U Bierbach |
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| Affiliation: | Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA. |
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| Abstract: | Platinum-acridine conjugates were prepared from [PtCl2(ethane-1,2-diamine)] and the novel acridinylthioureas MeHNC(S)NMeAcr (6) and MeHNC(S)NMe(CH2CH2)NHAcr (15) by replacing one chloro leaving group in the cisplatin analogue with thiourea sulfur. In HL-60 leukemia cells, IC(50) values for 7 (Pt-tethered 6) and 16 (Pt-tethered 15) were 75 and 0.13 microM, respectively. In the ovarian cell lines 2008 and C13, 16 was active at micromolar concentrations and showed only partial cross-resistance with clinical cisplatin. Possible structure-activity relationships are discussed. |
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