Novel adefovir mono L-amino acid ester, mono bile acid ester derivatives: Design, synthesis, biological evaluation, and molecular docking study

摘要

A series of adefovir mono L-amino acid ester, mono bile acid ester derivatives was designed and synthesized. The newly designed compounds have potent anti-anti-hepatitis B activity, especially compound 6c, which has more potent antiviral activity and a higher selectivity index (EC50 0.65 mu mol/L, SI 582.24) than adefovir dipivoxil. Uptake of compounds 6a-f into rat primary hepatocytes was 71.56, 63.92, 142.88, 104.25, 67.84, and 39.95-fold, respectively, higher than that of adefovir dipivoxil. In the presence of Na+, uptake of compounds 6a-c by Na+/taurocholate co-transporting polypeptide-Human embryonic kidney 293 cells was 128.5, 137.2 and 121.7-fold higher than that of adefovir dipivoxil. Potential binding modes of compounds 6a and 6c to human apical Na+-dependent bile acid transporter were also investigated.