ArticleACS medicinal chemistry letters2026
Negatively Charged Pronucleotides as Inhibitors of Glioma Cell Proliferation.
Article in ACS medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Three series of 5-fluoro-2'-deoxyuridine (FdU) nucleotide analogues were studied as potential antiglioma pronucleotides. The 5'-OH position was esterified with H-phosphonate, phosphate, and acylphosphate residues, all of which had negative charges. Additionally, some carried protecting groups of varying lipophilicity at the 3'-OH position. The acylphosphate moiety also contained different hydrocarbon substituents. The amphiphilic nature of these compounds should render them water-soluble and facilitate their permeation through the cell membranes. Inside the cell, they were expected to be converted to 5-fluoro-2'-deoxyuridine 5'-phosphate, a highly effective inhibitor of thymidylate synthetase. Two of the studied new FdU derivatives exhibited promising antiproliferative activity against the glioblastoma multiforme T98G cell line, an order of magnitude better than that of the parent nucleoside.
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