Synthesis, physicochemical properties, and cytotoxicity of a series of 5'-ester prodrugs of 5-iodo-2'-deoxyuridine.
Five aliphatic 5'-esters of 5-iodo-2'deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 microM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU.
Narurkar
M M
MM
Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Mitra
A K
AK
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D007065:Idoxuridine / Q000032:analysis / Q000138:chemical synthesis* / Q000633:toxicity; D010766:Phosphorylation; D011355:Prodrugs / Q000138:chemical synthesis*; D012995:Solubility; D014709:Vero Cells / Q000187:drug effects
D011355:Prodrugs; D007065:Idoxuridine