Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Oncology

Background:

• Nucleoside, nucleotide, and base analogs have a long history in treating viral infections and cancers.
• Over 20% of patients undergoing chemotherapy receive these analogs.
• This review focuses on analogs approved or in clinical development since 2000.

Purpose of the Study:

• To review the chemical synthesis and biological activity of anticancer nucleoside, nucleotide, and base analogs.
• To highlight cellular and clinical biology, drug resistance, and cancer-specific efficacy.
• To explore synthetic routes and scale-up processes for these analogs.

Main Methods:

• Literature review of FDA-approved and clinically developing anticancer nucleoside, nucleotide, and base analogs since 2000.
• Analysis of cellular and clinical biology, drug resistance mechanisms, and compound specificity.
• Examination of analog synthesis, including improved and scale-up methods.

Main Results:

• Detailed overview of anticancer analogs' chemical synthesis and biological mechanisms.
• Discussion on drug resistance and specificity across various cancer types.
• Exploration of synthetic advancements and large-scale production strategies.

Conclusions:

• Anticancer analogs remain vital in oncology, with ongoing research into their synthesis and application.
• Future directions include enhancing analog efficacy via prodrug strategies and combination therapies.
• Collaboration between medicinal chemists, biologists, and physicians is key to advancing analog-based cancer treatments.