Chiral-Modified Nucleoside Analogues: From Bioactivity to Therapeutic Applications

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Biochemistry

Background:

• Nucleosides are crucial in developing pharmaceuticals, chemotherapeutic agents, and bioregulators.
• Introducing chiral functionality into nucleosides can enhance selectivity for nucleos(t)ide-metabolizing enzymes and receptors.
• This modification can lead to more specific physiological activities and improved drug profiles.

Purpose of the Study:

• To explore the synthesis and application of modified nucleosides for enhanced pharmaceutical properties.
• To investigate how chiral modifications impact the selectivity and activity of nucleoside-based drugs.
• To identify novel nucleoside derivatives with potential antiviral and anticancer applications.

Main Methods:

• Chemical modification of the carbohydrate or heterocyclic base of nucleosides.
• Stereospecific enzymatic cleavage of nucleos(t)ide prodrugs.
• Synthesis of enantiomerically pure nucleosides with modifications at the ribose or heterocyclic base.

Main Results:

• A series of enantiomerically pure modified nucleosides were successfully synthesized.
• Novel compounds demonstrated antiviral or anticancer activity by inhibiting viral/cellular enzymes or activating cellular nucleoside kinases.
• Several derivatives showed enhanced ligand-receptor interactions, targeting the purinergic signaling system.
• Prototypes for treating viral infections, including SARS-CoV, SFTSV, dengue, HCV, RSV, and HMPV, were identified.

Conclusions:

• Direct modification of nucleosides with chiral functionalities is a viable strategy to increase drug efficacy, specificity, and selectivity.
• This approach holds significant promise for developing next-generation nucleoside-based therapeutics.
• Further research into structure-activity relationships can optimize these modified nucleosides for various medical applications.