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

被引：134

作者：

Martins, ET

Baruah, H

Kramarczyk, J

Saluta, G

Day, CS

Kucera, GL

Bierbach, U ^{[1
]}

机构：

[1] Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA

[2] Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27157 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 25期

关键词：

D O I：

10.1021/jm010293m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

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页码：4492 / 4496

页数：5

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