Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs.
Evaluation of fluorophore-tethered platinum complexes to monitor the fate of cisplatin analogs.
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DOI：
10.1007/s00775-015-1290-2
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发表时间：
2015-10
影响因子：
3
通讯作者：
Hall, Matthew D.
中科院分区：
文献类型：
--
作者：
Jagodinsky, Justin C.;Sulima, Agnieszka;Cao, Yiqi;Poprawski, Joanna E.;Blackman, Burchelle N.;Lloyd, John R.;Swenson, Rolf E.;Gottesman, Michael M.;Hall, Matthew D.
铂类药物顺铂、卡铂和奥沙利铂在临床中被广泛使用，因此在实验室环境中被广泛研究，有时通过生成荧光团标记的类似物。在这里，我们合成了两个含有乙烷-1,2-二胺配体与BODIPY荧光基团连接的Pt（II）配合物，并将它们的生物活性与先前报道的结合羧基荧光素和羧基荧光素二乙酸酯的Pt（II）配合物进行了比较。与顺铂比较pt -荧光团复合物的细胞毒性和dna损伤能力，发现Pt-BODIPY复合物在顺铂耐药细胞中具有更强的细胞毒性和更低的细胞毒性。显微镜显示主要是细胞质定位，核分布在较高浓度。从亲本细胞和耐药细胞生长的球形细胞显示Pt-BODIPY渗透到球体中，并保留顺铂耐药球形表型。虽然Pt-BODIPY复合物的大部分活性谱被保留，但耐药细胞中的积累仅受到轻微影响，这表明pt -荧光团细胞药理学的某些方面偏离了顺铂。
The platinum drugs cisplatin, carboplatin, and oxaliplatin are highly utilized in the clinic and as a consequence have been extensively studied in the laboratory setting, sometimes by generating fluorophore-tagged analogs. Here, we synthesized two Pt(II) complexes containing ethane-1,2-diamine ligands linked to a BODIPY fluorophore, and compared their biological activity with previously reported Pt(II) complexes conjugated to carboxyfluorescein and carboxyfluorescein diacetate. The cytotoxicity and DNA-damage capacity of Pt-fluorophore complexes was compared to cisplatin, and the Pt-BODIPY complexes were found to be more cytotoxic with reduced cytotoxicity in cisplatin-resistant cells. Microscopy revealed a predominately cytosolic localization, with nuclear distribution at higher concentrations. Spheroids grown from parent and resistant cells revealed penetration of Pt-BODIPY into spheroids, and retention of the cisplatin-resistant spheroid phenotype. While most activity profiles were retained for the Pt-BODIPY complexes, accumulation in resistant cells was only slightly affected, suggesting that some aspects of Pt-fluorophore cellular pharmacology deviate from cisplatin.
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影响因子：
8.8
作者：
Jones, A C;Stratford, I J;Wilson, P A;Peckham, M J
通讯作者：
Peckham, M J
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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