Monofunctional platinum(II) compounds and nucleolar stress: is phenanthriplatin unique?
Monofunctional platinum(II) compounds and nucleolar stress: is phenanthriplatin unique?
复制标题
DOI：
10.1007/s00775-019-01707-9
复制
发表时间：
2019-09
期刊：
影响因子：
--
通讯作者：
DeRose VJ
中科院分区：
文献类型：
--
作者：
McDevitt CE;Yglesias MV;Mroz AM;Sutton EC;Yang MC;Hendon CH;DeRose VJ
铂类抗癌药物广泛用于各种化疗方案。最近的研究表明，奥沙利铂和菲铂的细胞毒性是通过诱导核糖体生物合成应激途径，将其与顺铂和其他主要通过DNA损伤反应机制发挥作用的化合物区分开来。为了探测菲铂引起核仁应激的能力中的结构-活性关系，使用A549细胞通过核磷蛋白（NPM 1）再定位测定来测试一系列在环数、大小和取向上不同的单官能铂（II）化合物。发现菲铂在这些化合物中诱导NPM 1再定位是独特的。为了解释潜在的原因，对所有化合物进行空间体积、铂（II）-化合物表面长度和疏水性的计算预测。在测试的单官能铂（II）化合物中，菲铂具有最高的计算疏水性和体积，但没有表现出从铂（II）到表面的最大距离。因此，由第三芳环的存在引起的空间取向和/或疏水性可能是菲铂引起核仁应力的能力的重要因素。
Platinum anticancer therapeutics are widely used in a variety of chemotherapy regimens. Recent work has revealed that the cytotoxicity of oxaliplatin and phenanthriplatin is through induction of ribosome biogenesis stress pathways, differentiating them from cisplatin and other compounds that mainly work through DNA damage response mechanisms. In order to probe the structure-activity relationships in phenanthriplatin’s ability to cause nucleolar stress, a series of monofunctional platinum(II) compounds differing in ring number, size and orientation were tested by nucleophosmin (NPM1) relocalization assays using A549 cells. Phenanthriplatin was found to be unique among these compounds in inducing NPM1 relocalization. To decipher underlying reasons, computational predictions of steric bulk, platinum(II)-compound surface length and hydrophobicity were performed for all compounds. Of the monofunctional platinum(II) compounds tested, phenanthriplatin has the highest calculated hydrophobicity and volume but does not exhibit the largest distance from platinum(II) to the surface. Thus, spatial orientation and/or hydrophobicity caused by the presence of a third aromatic ring may be significant factors in the ability of phenanthriplatin to cause nucleolar stress.
登录
查看更多内容
影响因子：
15
作者：
Johnstone TC;Lippard SJ
通讯作者：
Lippard SJ
影响因子：
3.7
作者：
Kresse, G;Furthmuller, J
通讯作者：
Furthmuller, J
影响因子：
15
作者：
Kellinger MW;Park GY;Chong J;Lippard SJ;Wang D
通讯作者：
Wang D
影响因子：
3
作者：
Rueden CT;Schindelin J;Hiner MC;DeZonia BE;Walter AE;Arena ET;Eliceiri KW
通讯作者：
Eliceiri KW
影响因子：
3.7
作者：
BLOCHL, PE
通讯作者：
BLOCHL, PE