Tisnerat Camille, Di Ciano Samuele, Pertusati Fabrizio, Serpi Michaela
School of Chemistry, Cardiff University, Main Building, Park Place, CF10 3AT Cardiff, Wales, United Kingdom.
School of Pharmacy and Pharmaceutical Sciences, Redwood Building, King Edwards VII Avenue, CF10 3NB, Cardiff, Wales, United Kingdom.
Org Lett. 2025 Jan 10;27(1):322-327. doi: 10.1021/acs.orglett.4c04379. Epub 2024 Dec 17.
In this study, we report for the first time a microwave-accelerated synthesis of purine and pyrimidine nucleoside triphosphate prodrugs, whose γ phosphate is masked with an aryloxy moiety and an amino acid ester (γ-ProTriP). The synthetic utility of this method is illustrated by the synthesis of triphosphate prodrugs of clofarabine and gemcitabine, two FDA-approved anticancer drugs. These new prodrugs showed good chemical and rat serum stability. Remarkably the clofarabine prodrug showed significant cytotoxicity against a panel of cancer cell lines.
在本研究中,我们首次报道了一种微波加速合成嘌呤和嘧啶核苷三磷酸前药的方法,其γ磷酸基团被芳氧基部分和氨基酸酯(γ-ProTriP)所掩盖。通过合成两种美国食品药品监督管理局(FDA)批准的抗癌药物氯法拉滨和吉西他滨的三磷酸前药,说明了该方法的合成实用性。这些新前药表现出良好的化学稳定性和大鼠血清稳定性。值得注意的是,氯法拉滨前药对一组癌细胞系显示出显著的细胞毒性。