1. Lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs: A versatile drug delivery paradigm.
- Author
-
Zhang Y, Fan C, Zhang J, Tian X, Zuo W, and He K
- Subjects
- Humans, Animals, Drug Delivery Systems, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Molecular Structure, Organophosphonates chemistry, Organophosphonates pharmacology, Prodrugs chemistry, Prodrugs pharmacology, Prodrugs chemical synthesis, Lipids chemistry, Nucleosides chemistry, Nucleosides pharmacology, Nucleosides chemical synthesis
- 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF