ProTides of BVdU as potential anticancer agents upon efficient intracellular delivery of their activated metabolites.

ABSTRACT: Nucleosides represent a major chemotherapeutic class for treating cancer, however their limitations in terms of cellular uptake, nucleoside kinase-mediated activation and catabolism are well-documented. The monophosphate pro-nucleotides known as ProTides represents a powerful strategy for bypassing the dependence on active transport and nucleoside kinase-mediated activation. Herein, we report the structural tuning of BVdU ProTides. Forty six phosphoramidates were prepared and biologically evaluated against three different cancer cell lines; murine leukemia (L1210), human CD₄⁺ T-lymphocyte (CEM) and human cervical carcinoma (HeLa). Twenty-fold potency enhancement compared to BVdU was achieved against L1210 cells. Interestingly, a number of ProTides showed low micromola

SUBMITTER: Kandil S 

PROVIDER: S-EPMC5131913 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature