Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), CNRS, Univ Paris Sud, Université Paris-Saclay, 15 rue Georges Clemenceau, 91405 Orsay Cedex, France.
Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), CNRS, Univ Paris Sud, Université Paris-Saclay, 15 rue Georges Clemenceau, 91405 Orsay Cedex, France.
Bioorg Chem. 2019 Oct;91:103158. doi: 10.1016/j.bioorg.2019.103158. Epub 2019 Jul 24.
This study describes the synthesis of arylboronate-based ROS-responsive prodrugs of doxorubicin and their biological evaluation as anticancer agents. The determination of the most sensitive cancer type toward arylboronate prodrugs is crucial for further consideration of these molecules in clinical phase. To address this goal, an arylboronate-based profluorescent probe was used to compare the capacity of various cancer cell lines to efficiently convert the precursor into the free fluorophore. On the selected MiaPaCa-2 pancreatic cancer cells, a benzeneboronate prodrug exhibited 67% of the cytotoxicity obtained with the free doxorubicin. The prodrug was also able to induce tumor regression on MiaPaCa-2 pancreatic tumor model in ovo. Using this model, the amount of free doxorubicin liberated from this prodrug into the tumor was equivalent to the quantity measured after direct intratumoral injection of the same concentration of doxorubicin.
本研究描述了阿霉素基于硼酸酯的活性氧响应前药的合成及其作为抗癌剂的生物学评价。确定对硼酸酯前药最敏感的癌症类型对于这些分子在临床阶段的进一步考虑至关重要。为了实现这一目标，使用基于硼酸酯的荧光探针来比较各种癌细胞系将前体有效转化为游离荧光团的能力。在选定的 MiaPaCa-2 胰腺癌细胞中，苯硼酸酯前药表现出与游离阿霉素相当的 67%的细胞毒性。该前药还能够在鸡胚中的 MiaPaCa-2 胰腺肿瘤模型中诱导肿瘤消退。使用该模型，从该前药中释放到肿瘤中的游离阿霉素的量与直接瘤内注射相同浓度的阿霉素后测量到的量相当。
