Design, synthesis, and biological activity of a novel non-cisplatin-type platinum-acridine pharmacophore
Design, synthesis, and biological activity of a novel non-cisplatin-type platinum-acridine pharmacophore
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DOI：
10.1021/jm010293m
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发表时间：
2001-12-06
影响因子：
7.3
通讯作者：
Bierbach, U
中科院分区：
文献类型：
--
作者：
Martins, ET;Baruah, H;Bierbach, U
用硫脲硫取代顺铂类似物中的一个氯离去基团，由[PtCl_2（乙烷-1，2-二胺）]和新的吖啶基硫脲MeHNC（S）NMeAcr（6）和MeHNC（S）NMe（CH_2CH_2）NHAcr（15）制备铂-吖啶缀合物。在HL-60白血病细胞中，7（Pt-tethered 6）和16（Pt-tethered 15）的IC 50值分别为75和0.13 μ M。在卵巢细胞系2008和C13* 中，16在微摩尔浓度下具有活性，并且仅显示出与临床顺铂的部分交叉抗性。可能的结构-活性关系进行了讨论。
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.