Dataset Information

Design and synthesis of vidarabine prodrugs as antiviral agents.

ABSTRACT: 5'-O-D- and L-amino acid derivatives and 5'-O-(D- and L-amino acid methyl ester phosphoramidate) derivatives of vidarabine (ara-A) were synthesized as vidarabine prodrugs. Some compounds were equi- or more potent in vitro than vidarabine against two pox viruses and their uptake by cultured cells was improved compared to the parent drug.

SUBMITTER: Shen W

PROVIDER: S-EPMC2642980 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Design and synthesis of vidarabine prodrugs as antiviral agents.

Shen Wei W Kim Jae-Seung JS Kish Phillip E PE Zhang Jie J Mitchell Stefanie S Gentry Brian G BG Breitenbach Julie M JM Drach John C JC Hilfinger John J

Bioorganic & medicinal chemistry letters 20081210 3

5'-O-D- and L-amino acid derivatives and 5'-O-(D- and L-amino acid methyl ester phosphoramidate) derivatives of vidarabine (ara-A) were synthesized as vidarabine prodrugs. Some compounds were equi- or more potent in vitro than vidarabine against two pox viruses and their uptake by cultured cells was improved compared to the parent drug. ...[more]

PMID: 19097789

Similar Datasets

Project description:The double-stranded DNA (dsDNA) viruses represented by adenovirus and monkeypox virus, have attracted widespread attention due to their high infectivity. In 2022, the global outbreak of mpox (or monkeypox) has led to the declaration of a Public Health Emergency of International Concern. However, to date therapeutics approved for dsDNA virus infections remain limited and there are still no available treatments for some of these diseases. The development of new therapies for treating dsDNA infection is in urgent need. In this study, we designed and synthesized a series of novel disulfide-incorporated lipid conjugates of cidofovir (CDV) as potential candidates against dsDNA viruses including vaccinia virus (VACV) and adenovirus (AdV) 5. The structure-activity relationship analyses revealed that the optimum linker moiety was C2H4 and the optimum aliphatic chain length was 18 or 20 atoms. Among the synthesized conjugates, 1c exhibited more potency against VACV (IC50 = 0.0960 μM in Vero cells; IC50 = 0.0790 μM in A549 cells) and AdV5 (IC50 = 0.1572 μM in A549 cells) than brincidofovir (BCV). The transmission electron microscopy (TEM) images revealed that the conjugates could form micelles in phosphate buffer. The stability studies in the GSH environment demonstrated that the formation of micelles in phosphate buffer might protect the disulfide bond from glutathione (GSH) reduction. The dominant means of the synthetic conjugates to liberate the parent drug CDV was by enzymatic hydrolysis. Furthermore, the synthetic conjugates remained sufficiently stable in simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and pooled human plasma, which indicated the possibility for oral administration. These results indicated 1c may be a broad-spectrum antiviral candidate against dsDNA viruses with potential oral administration. Moreover, modification of the aliphatic chain attached to the nucleoside phosphonate group was involved as an efficient prodrug strategy for the development of potent antiviral candidates.

Dataset Information

Design and synthesis of vidarabine prodrugs as antiviral agents.

Publications

Design and synthesis of vidarabine prodrugs as antiviral agents.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets