Sergheraert C, Pierlot C, Tartar A, Henin Y, Lemaitre M
Faculté de Pharmacie, Institut Pasteur de Lille, URA CNRS 1309, Lille, France.
J Med Chem. 1993 Apr 2;36(7):826-30. doi: 10.1021/jm00059a006.
Several 5-monophosphate D4T derivatives and their analogues were synthesized as potential lipophilic prodrugs of D4T. Cholesteryl D4T phosphate diester and bis-5'-D4T phosphate inhibited HIV replication in CEM-Cl13 cells more efficiently than D4T itself as measured by the inhibition of cytopathic effect based on MTT assay or reverse transcriptase activity. The two compounds were devoid of toxicity on CEM-Cl13 cells at doses equal to 50 and 100 microM, respectively, which brought the selectivity index into the same range as AZT.
合成了几种5-单磷酸双脱氧胸苷（D4T）衍生物及其类似物，作为D4T潜在的亲脂性前药。通过基于MTT法的细胞病变效应抑制或逆转录酶活性测定，胆固醇基D4T磷酸二酯和双-5'-D4T磷酸酯在CEM-Cl13细胞中抑制HIV复制的效率比D4T本身更高。这两种化合物在分别等于50和100微摩尔的剂量下对CEM-Cl13细胞无毒性，这使得选择性指数与齐多夫定（AZT）处于相同范围。
