Design, synthesis, and biological activity of a novel non-cisplatin-type platinum-acridine pharmacophore

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, IC50 values for 7 (Pt-tethered 6) and 16 (Pt-tethered 15) were 75 and 0.13 muM, 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.