Fluorescent Cisplatin Analogues and Cytotoxic Activity

顺铂 细胞毒性 荧光 化学 DNA 细胞培养 生物化学 组合化学 体外 生物 化疗 遗传学 量子力学 物理
作者
Emilio Rodríguez-Fernández,J. Manzano,A. Alonso,M.J. Almendral,Martín Pérez‐Andres,Alberto Órfão,José María Criado
出处
期刊:Current Medicinal Chemistry [Bentham Science]
卷期号:16 (32): 4314-4327 被引量:13
标识
DOI:10.2174/092986709789578169
摘要

Cisplatin is one of the chemotherapeutic agents used the most for testicular, ovarian and several other cancers. In order to overcome cisplatin resistance, other platinum (Pt) compounds have been developed and, in the last ten years, Pt-derivatives with reporting activity have also been synthesized. The first generation of reporting Pt-compounds was based on linking a fluorescent molecule (e.g. cyanine) to cisplatin, but more recent studies have focused on strategies to synthesize intrinsically fluorescent derivatives. Accordingly, bile acid Pt-compounds have shown fluorescence intensity that is stable at room temperature for a long time; this fluorescence is maintained after binding to oligonucleotides or DNA. Because of this, the binding mode of these compounds to DNA can be easily analyzed both by flow injection and fluorescence techniques, showing that although these compounds target the nuclei, they form adducts with the DNA that are different from those due to cisplatin. In line with this, these bile acid derivatives have shown increased cytotoxicity and ability to overcome resistance as compared to cisplatin in several cell lines. Moreover, in contrast to cisplatin, the activity of these compounds does not seem to be restricted to cycling cells but they also seem to kill resting cells. This review summarizes the information available on reporting Pt-compounds and focuses on these novel, intrinsically fluorescent bile acid Pt derivatives, their biochemical characteristics and biological activity.

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