Curcumin analogues with improved antioxidant properties: A theoretical exploration

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Biochemistry

Background:

• Curcumin, a dietary molecule, possesses significant antioxidant properties.
• Oxidative stress, driven by free radicals, contributes to various health issues.
• Understanding the radical scavenging mechanisms of antioxidants is crucial.

Purpose of the Study:

• To computationally analyze the antioxidant activity of curcumin and its analogues (hispolon, halfcurcumin, polyhydroxycurcumin).
• To investigate the radical scavenging potential using density functional theory (DFT).
• To explore interactions with pro-oxidant enzymes via molecular docking.

Main Methods:

• Density Functional Theory (DFT) calculations were employed to determine thermochemical parameters like Bond Dissociation Enthalpy (BDE).
• Hydrogen Atom Transfer (HAT) energetics were explored for hydroxyl groups against hydroxyl (•OH) and hydroperoxyl (•OOH) radicals in gas and solvent phases.
• Molecular docking studies were performed to assess interactions with xanthine oxidase.

Main Results:

• Hispolon and polyhydroxycurcumin, featuring ortho dihydroxy arrangements, demonstrated superior radical scavenging capabilities.
• Halfcurcumin exhibited antioxidant activity comparable to curcumin.
• Calculated absorption properties aligned well with experimental data, and docking revealed potential indirect oxidative stress control via xanthine oxidase inhibition.

Conclusions:

• Hispolon and polyhydroxycurcumin are identified as highly effective radical scavengers.
• The computational approach provides valuable insights into the antioxidant mechanisms of these curcuminoids.
• These antioxidants may play a role in mitigating oxidative stress through enzyme interactions.