Lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs: A versatile drug delivery paradigm.
Eur J Med Chem
; 275: 116614, 2024 Sep 05.
Article
in En
| MEDLINE
| ID: mdl-38925014
ABSTRACT
Integrating lipid conjugation strategies into the design of nucleoside monophosphate and monophosphonate prodrugs is a well-established approach for discovering potential therapeutics. The unique prodrug design endows nucleoside analogues with strong lipophilicity and structures resembling lysoglycerophospholipids, which improve cellular uptake, oral bioavailability and pharmacological activity. In addition, the metabolic stability, pharmacological activity, pharmacokinetic profiles and biodistribution of lipid prodrugs can be finely optimized by adding biostable caps, incorporating transporter-targeted groups, inserting stimulus-responsive bonds, adjusting chain lengths, and applying proper isosteric replacements. This review summarizes recent advances in the structural features and application fields of lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs. This collection provides deep insights into the increasing repertoire of lipid prodrug development strategies and offers design inspirations for medicinal chemists for the development of novel chemotherapeutic agents.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prodrugs
/
Lipids
/
Nucleosides
Limits:
Animals
/
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2024
Document type:
Article