Тhio-containing pteridines: Synthesis, modification, and biological activity

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Pharmacology

Background:

• Pteridine derivatives are known for diverse biological activities.
• Novel thio-containing pteridines offer potential as therapeutic agents.
• Understanding structure-activity relationships is crucial for drug discovery.

Purpose of the Study:

• To synthesize novel thio-containing pteridines.
• To evaluate their inhibitory activity against dihydrofolate reductase (DHFR).
• To assess their antiradical activity.

Main Methods:

• Condensation reactions for pteridine synthesis.
• In silico docking studies for DHFR active site affinity prediction.
• In vitro enzyme inhibition assays (DHFR).
• Antioxidant activity assays (DPPH assay).

Main Results:

• Successfully synthesized a series of novel thio-containing pteridines.
• In silico analysis showed comparable DHFR affinity to methotrexate.
• In vitro DHFR inhibition was observed, but less potent than methotrexate.
• Compounds 5.1 and 5.3 exhibited significant antiradical activity, exceeding ascorbic acid.

Conclusions:

• The synthesized thio-containing pteridines represent a promising scaffold for developing new biologically active agents.
• Structure-activity relationship data guides further optimization for enhanced DHFR inhibition and antiradical effects.
• These compounds warrant further investigation for potential therapeutic applications.