含联吡啶非离去基团修饰的铂-吖啶杂化剂的合成与生物学评价
Synthesis and biological evaluation of platinum-acridine hybrid agents modified with bipyridine non-leaving groups.
作者信息
Kheradi Alexander R, Saluta Gilda, Kucera Gregory L, Day Cynthia S, Bierbach Ulrich
机构信息
Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
出版信息
Bioorg Med Chem Lett. 2009 Jul 1;19(13):3423-5. doi: 10.1016/j.bmcl.2009.05.046. Epub 2009 May 18.
Abstract
The use of 2,2'-bipyridines (4,4'-R(2)-2,2'-bpy; R=H, Me, OMe, CF(3)) as non-leaving groups (L-L) in platinum-acridinylthiourea conjugates, PtCl(L-L)(ACRAMTU)(2), has been investigated. All bpy-substituted complexes (2-5) show micromolar activity in HL-60 (leukemia) and H460 (lung) cancer cell lines but proved to be significantly less potent than the prototypical compound (1) containing aliphatic ethane-1,2-diamine. NMR and mass spectrometry data indicate that bpy accelerates the reaction of platinum with DNA nitrogen, but the resulting adducts are more labile than those formed by the prototype.
摘要
研究了在铂-吖啶基硫脲共轭物PtCl(L-L)(ACRAMTU)₂中使用2,2'-联吡啶（4,4'-R(2)-2,2'-bpy；R = H、Me、OMe、CF₃）作为非离去基团（L-L）的情况。所有联吡啶取代的配合物（2-5）在HL-60（白血病）和H460（肺癌）癌细胞系中均表现出微摩尔活性，但事实证明其效力明显低于含有脂肪族乙烷-1,2-二胺的原型化合物（1）。核磁共振和质谱数据表明，联吡啶加速了铂与DNA氮的反应，但生成的加合物比原型形成的加合物更不稳定。
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