Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Department of Pharmacology & The Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Neurosurgical Research Unit, The Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Bioorg Med Chem Lett. 2020 Jul 15;30(14):127252. doi: 10.1016/j.bmcl.2020.127252. Epub 2020 May 8.
We describe the synthesis and in vitro activity of drug-dye conjugate 1, which is a combination of the PARP inhibitor rucaparib and heptamethine cyanine dye IR-786. The drug-dye conjugate 1 was evaluated in three different patient-derived glioblastoma cell lines and showed strong cytotoxic activity with nanomolar potency (EC: 128 nM), which was a 780 fold improvement over rucaparib itself. We also observe a synergistic effect of 1 with temozolomide (TMZ), the standard drug for treatment for glioblastoma even though these cell lines were resistant to TMZ treatment. We envisage such conjugates to be worth exploring for their utility in the treatment of various brain cancers.
我们描述了药物-染料偶联物 1 的合成和体外活性，它是 PARP 抑制剂 rucaparib 和七甲川花菁染料 IR-786 的组合。该药物-染料偶联物 1 在三种不同的源自患者的脑胶质瘤细胞系中进行了评估，表现出具有纳摩尔效力（EC：128 nM）的强烈细胞毒性活性，比 rucaparib 本身提高了 780 倍。我们还观察到 1 与替莫唑胺（TMZ）的协同作用，TMZ 是治疗脑胶质瘤的标准药物，尽管这些细胞系对 TMZ 治疗有抗性。我们预计这些偶联物在治疗各种脑癌方面具有实用价值。
