Ring-expanded ("Fat") nucleosides as broad-spectrum anticancer and antiviral agents

Area of Science:

• Medicinal Chemistry
• Biochemistry
• Pharmacology

Background:

• Ring-expanded nucleosides (RENs) are purine nucleoside analogs with a fused imidazodiazepine or imidazotriazepine ring system.
• Both natural and synthetic RENs are of significant chemical, biochemical, biophysical, and medicinal interest.
• Natural RENs like coformycin and pentostatin are known enzyme inhibitors with potential therapeutic applications.

Purpose of the Study:

• To review the chemical structures, origins, and biological activities of RENs.
• To highlight the therapeutic potential of RENs as antiviral and antitumor agents.
• To discuss the challenges and future prospects of RENs in clinical applications.

Main Methods:

• Literature review of natural and synthetic RENs.
• Analysis of enzyme inhibition mechanisms.
• Evaluation of in vitro and in vivo biological activities.
• Assessment of toxicity profiles.

Main Results:

• Natural RENs, potent enzyme inhibitors, often exhibit high toxicity, limiting clinical use, with pentostatin being a notable exception for leukemia and lymphoma treatment.
• Synthetic RENs display promising antitumor and antiviral activities against a range of cancers and viruses with minimal host cell toxicity.
• Preliminary in vitro studies show RENs are effective against prostate and breast cancer cells, warranting further investigation.

Conclusions:

• RENs represent a promising class of compounds for developing novel chemotherapeutic agents against cancer and viral infections.
• Synthetic RENs offer a favorable therapeutic window due to their targeted activity and reduced toxicity.
• Further research and clinical trials are essential to fully realize the therapeutic potential of RENs.