Supplementary Material for: Curcumin Derivatives as Allosteric Modulator of Α7-Nachr: Functional and Molecular Docking Insights

Background: Curcumin has emerged as promising candidate for therapeutic modulation of neurodegenerative disorders by acting on α7-nicotinic acetylcholine receptors (α7-nAChR). Objective: This study aims to evaluate the potential of Curcumin metabolites and derivatives as positive allosteric modulators (PAMs) of α7-nAChR. Materials and Methods: Functional properties of α7-nAChR were assessed using two-electrode voltage clamp techniques in Xenopus oocytes, and molecular docking studies were employed to identify high-affinity binding sites. Results: The findings reveal that Curcumin metabolites and derivatives also potentiate α7-nAChR and interact with a common transmembrane domain binding site on α7-nAChR, demonstrating potent modulatory effects. Notably, these derivatives exhibit superior binding energies compared to the established PAM PNU-120596. Conclusion: The study underscores the therapeutic potential of Curcumin metabolites and derivatives as receptor-specific natural agents for managing neurodegenerative and inflammatory diseases.