Amino Acid Ester Prodrugs of the Antiviral Agent 2-Bromo-5,6-dichloro-1-(β-d-ribofuranosyl)benzimidazole as Potential Substrates of hPEPT1 Transporter

Amino acid ester prodrugs of 2-bromo-5,6-dichloro-1-(β-d-ribofuranosyl)benzimidazole (BDCRB) were synthesized and evaluated for their affinity for hPEPT1, an intestinal oligopeptide transporter. Assays of competitive inhibition of [3H]glycylsarcosine (Gly-Sar) uptake in HeLa/hPEPT1 cells by the amino acid ester prodrugs of BDCRB suggested their 2- to 4-fold higher affinity for hPEPT1 compared to BDCRB. Further, promoieties with hydrophobic side chains and l-configuration were preferred by the hPEPT1 transporter.