Bio-organic Chemistry Laboratory, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada; Department of Chemistry, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
Bioorg Med Chem Lett. 2020 Mar 15;30(6):126983. doi: 10.1016/j.bmcl.2020.126983. Epub 2020 Jan 21.
A synthetic strategy to access a novel family of nucleoside analogues bearing a C3'-nitrile substituted all-carbon quaternary center is presented herein. These purine bearing scaffolds were tested in two pancreatic cancer cell lines harboring either wild-type (BxPC3) or G12V KRAS (Capan2) mutations. A promising compound was shown to have significantly greater efficacy in the Capan2 cell line as compared to Gemcitabine, the clinical gold standard used to treat pancreatic cancer.
本文提出了一种合成方法，可以获得一类新型的核苷类似物，这些类似物在 C3'位具有氰基取代的全碳季碳原子。这些含有嘌呤的支架在两种胰腺癌细胞系中进行了测试，这两种细胞系分别携带野生型（BxPC3）或 G12V KRAS（Capan2）突变。与用于治疗胰腺癌的临床金标准药物吉西他滨相比，一种有前景的化合物在 Capan2 细胞系中显示出显著更高的疗效。
