Repurposing of Potential Curcumin Derivatives Against Cyclooxygenase-2 Using In Silico Methods and Its Implications...

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• Cyclooxygenase-2 (COX-2) is integral to inflammatory pathways and neuroinflammation in neurological conditions like Alzheimer's disease.
• Current COX-2 inhibitors (coxibs) have limitations, driving the search for safer alternatives.
• Curcumin derivatives have shown potential in previous computational studies for enzyme interactions.

Purpose of the Study:

• To investigate the potential of 2561 curcumin derivatives as selective COX-2 inhibitors.
• To evaluate their binding affinity and interactions with COX-2 using computational methods.
• To explore their therapeutic potential for neuroinflammatory disorders.

Main Methods:

• In silico screening of 2561 curcumin derivatives against the COX-2 enzyme.
• Molecular docking to assess binding affinities and interactions with key COX-2 regions.
• Molecular dynamics simulations to evaluate complex stability and interactions.

Main Results:

• Five curcumin derivatives exhibited strong binding affinities to COX-2, with energies around -10.7 kcal/mol.
• Molecular dynamics simulations confirmed stable complexes with consistent hydrogen bonds and hydrophobic interactions.
• Energy calculations indicated energetically favorable binding, suggesting therapeutic potential.

Conclusions:

• Several curcumin derivatives demonstrate significant potential as COX-2 inhibitors.
• These compounds represent promising candidates for developing new treatments for neuroinflammatory conditions.
• Further in vitro and in vivo studies are warranted to validate efficacy and safety.