| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1392994 | European Journal of Medicinal Chemistry | 2012 | 8 Pages |
A series of phosphonate ester prodrugs of adefovir incorporating l-amino (thio)acid and non-steroidal anti-inflammatory drug (NSAID) moieties were synthesized and their anti-HBV activity and renal cell toxicity were evaluated in HepG2 2.2.15 and HK-2 cells respectively. Bioactivity evaluation results revealed that this kind of adefovir prodrug have lower renal cell toxicity than adefovir dipivoxil. Compounds 8a and 8b, incorporating the NSAID ketoprofen and the l-amino acid (Val or Ile) structural fragments, exhibited more potent anti-HBV activity than adefovir dipivoxil with IC50 = 0.51 and 0.73 μM, SI = 1697.64 and 881.92 respectively. In vitro stability studies showed that the synthesized prodrugs have higher chemical and plasma stability than the positive control adefovir dipivoxil.
Graphical abstractA series of phosphonate ester prodrugs of adefovir incorporating l-amino (thio)acid and non-steroidal anti-inflammatory drug (NSAID) moieties were synthesized, characterized and evaluated for their anti-HBV activity, renal cell toxicity and in vitro stability.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of novel mixed phosphonate prodrugs of adefovir were prepared. ► Compounds 8a and 8b displayed more potent anti-HBV activity than adefovir dipivoxil. ► Designed compounds exhibited lower renal cell toxicity than adefovir dipivoxil. ► Designed compounds have higher stability than adefovir dipivoxil.
