COX-1 Inhibitors: Beyond Structure Toward Therapy.

Area of Science:

• Biochemistry and Pharmacology
• Cancer Biology
• Drug Discovery

Background:

• Prostaglandin biosynthesis involves cyclooxygenase (COX), with COX-1 and COX-2 isoforms.
• Arachidonic acid (AA) release from cell membranes triggers neopathological processes.
• COX inhibitors modulate these pathways, impacting disease onset and progression.

Purpose of the Study:

• To review recent advancements in identifying highly selective COX-1 inhibitors.
• To explore the theranostic potential of these inhibitors in neuroinflammation and ovarian cancer.
• To discuss the gastrotoxic effects associated with COX-1 inhibition.

Main Methods:

• Classification of COX-1 inhibitors based on chemical structures of synthetic and natural compounds.
• Investigation of molecular interactions using X-ray crystallography, mutagenesis, assays, and docking.
• Development of pharmacometric predictive models for inhibitor design.

Main Results:

• Five classes of COX-1 inhibitors have been identified.
• High levels of COX-1 expression are observed in human epithelial ovarian cancer, suggesting its role in progression.
• Selective COX-1 inhibitors show potential as active pharmaceutical ingredients for therapeutic protocols.

Conclusions:

• Highly selective COX-1 inhibitors, both synthetic and plant-derived, have been identified.
• These inhibitors hold promise for theranostic applications in ovarian cancer and neuroinflammation.
• Further research is warranted to optimize their therapeutic efficacy and safety profile.