Application of the cycloSal-prodrug approach for improving the biological potential of phosphorylated biomolecules.
Pronucleotides represent a promising tool to improve the biological activity of nucleoside analogs in antiviral and cancer chemotherapy. The cycloSal-approach is one of several conceptually different pronucleotide systems. This approach can be applied to various nucleoside analogs. A salicyl alcohol as a cyclic bifunctional masking unit is used, and shown to afford a chemically driven release of the particular nucleotide from the lipophilic phosphate triester precursor molecule. A conceptual extension of the cycloSal-approach results in the design of "lock-in"-cycloSal-derivatives. The cycloSal-approach is not restricted to the delivery of bioactive nucleotides but also useful for the intracellular delivery of hexose-1-phosphates.
Meier
C
C
Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany. chris.meier@chemie.uni-hamburg.de
Balzarini
J
J
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D054306:Dideoxynucleotides; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D009711:Nucleotides / Q000737:chemistry* / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology; D012459:Salicylates / Q000737:chemistry* / Q000494:pharmacology; D018119:Stavudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013942:Thymine Nucleotides
D000998:Antiviral Agents; C415254:Cyclosaligenyl-2',3'-didehydro-2',3'-dideoxythymidine monophosphate; D054306:Dideoxynucleotides; D009711:Nucleotides; D011355:Prodrugs; D012459:Salicylates; D013942:Thymine Nucleotides; D018119:Stavudine