Synthesis and anti-HIV evaluation of D4T and D4T 5'-monophosphate prodrugs.
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.
Faculté de Pharmacie, Institut Pasteur de Lille, URA CNRS 1309, Lille, France.
C
C
Sergheraert
C
C
Pierlot
A
A
Tartar
Y
Y
Henin
M
M
Lemaitre
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054306:Dideoxynucleotides; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018119:Stavudine; D013329:Structure-Activity Relationship; D013942:Thymine Nucleotides; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D054306:Dideoxynucleotides; D011355:Prodrugs; D013942:Thymine Nucleotides; C080525:bis-5'-D4T phosphate; D018119:Stavudine