Design, Synthesis, and Biological Activity of a Novel Non-Cisplatin-type Platinum−Acridine Pharmacophore
- 9 November 2001
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 44 (25) , 4492-4496
- https://doi.org/10.1021/jm010293m
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, IC50 values for 7 (Pt-tethered 6) and 16 (Pt-tethered 15) were 75 and 0.13 μM, 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.Keywords
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