用于靶向癌症治疗的细胞毒性铁螯合剂的糖苷酶激活前药。
Glycosidase-activated prodrugs of a cytotoxic iron chelator for targeted cancer therapy.
作者信息
Tomar Debashish, Steinbrueck Axel, Sedgwick Adam C, Levine Matthew S, Sessler Jonathan L, Metzler-Nolte Nils
机构信息
Faculty of Chemistry and Biochemistry, Inorganic Chemistry I - Bioinorganic chemistry, Ruhr-University Bochum Universitaetsstrasse 150 44801 Bochum Germany
Department of Chemistry, University of Texas at Austin 105 E 24th street A5300 Austin TX 78712-1224 USA.
出版信息
RSC Med Chem. 2025 Jun 19. doi: 10.1039/d5md00232j.
New glycoside-prodrugs based on the iron chelator deferasirox were designed. Selective enzymatic activation by glycosidases was observed within 24 hours, accompanied by cancer cell-selective cytotoxicity. Notably, derivative 3a, bearing a β-d-galactose moiety, showed promising selective activity against galactosidase overexpressing OvCar-3 cells (IC 9.1 ± 1.6 μM) while maintaining low activity against fibroblast control GM5756 cells (IC > 100 μM).
设计了基于铁螯合剂地拉罗司的新型糖苷前药。在24小时内观察到糖苷酶的选择性酶促活化，并伴有癌细胞选择性细胞毒性。值得注意的是，带有β - d - 半乳糖部分的衍生物3a对过表达半乳糖苷酶的OvCar - 3细胞显示出有前景的选择性活性（IC 9.1 ± 1.6 μM），而对成纤维细胞对照GM5756细胞的活性较低（IC > 100 μM）。
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