新型非顺铂型铂-吖啶药效团的设计、合成及生物活性

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

作者信息

Martins E T, Baruah H, Kramarczyk J, Saluta G, Day C S, Kucera G L, Bierbach U

机构信息

Department of Chemistry, Wake Forest University, Winston-Salem, North Carolina 27109, USA.

出版信息

J Med Chem. 2001 Dec 6;44(25):4492-6. doi: 10.1021/jm010293m.

DOI:10.1021/jm010293m

PMID:11728195

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.

摘要

通过用硫脲硫取代顺铂类似物中的一个氯离去基团，由[PtCl2(乙二胺)]与新型吖啶基硫脲MeHNC(S)NMeAcr (6)和MeHNC(S)NMe(CH2CH2)NHAcr (15)制备了铂-吖啶共轭物。在HL-60白血病细胞中，7（铂连接的6）和16（铂连接的15）的IC(50)值分别为75和0.13 microM。在卵巢细胞系2008和C13中，16在微摩尔浓度下具有活性，并且与临床顺铂仅表现出部分交叉耐药性。讨论了可能的构效关系。