α-Halogenated Curcumins Enhance the Binding Affinity and Induced Structural Alterations to Amyloid-β Protein in Alzheimer’s Disease
6 affiliations
- 1Department of Life Sciences, College of Science, Alfaisal University, Riyadh 11533, Saudi Arabia
- 2College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- 3Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India
- 4Tissue/Organ Bioengineering & BioMEMS Laboratory, Organ Transplant Centre of Excellence (TR & I-Dept), King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia
- 5Department of Chemistry, Penn State Scranton, Dunmore, PA 18512, USA
- 6Department of Chemistry, College of Science, Alfaisal University, Riyadh 11533, Saudi Arabia
Abstract
Amyloid-β (Aβ) aggregation and associated structural changes are central features of Alzheimer’s disease (AD) pathology. In this study, we investigated the binding of α-halogenated curcumins, α-bromocurcumin and α-chlorocurcumin, to Aβ1-42 and examined their effects on the peptide secondary structure using fluorescence spectroscopy and circular dichroism (CD). Both α-halogenated curcumins interacted with Aβ1-42, but their binding properties differed from those of the parent curcumin. α-Chlorocurcumin exhibited a higher binding affinity for Aβ1-42 than curcumin, whereas α-bromocurcumin showed comparatively weaker binding. Temperature-dependent binding studies revealed that the association of α-halogenated curcumins with Aβ1-42 was influenced by temperature, with reduced binding affinity at higher temperatures. Thermodynamic analysis demonstrated favorable free-energy changes for the interactions and revealed that α-halogenation altered the relative enthalpic and entropic contributions to Aβ1-42 binding. CD analysis further showed that binding of the curcumin altered the secondary structure of Aβ1-42. These structural changes were more pronounced in the presence of the α-halogenated derivatives, indicating that halogen substitution influences the interaction and conformational response of Aβ1-42. Molecular docking analysis provided additional insight into the possible binding modes and predicted intermolecular contacts between the α-halogenated curcumin and Aβ1-42. Overall, the findings demonstrate that α-halogenation modulates the binding and structural effects of curcumin derivatives on Aβ1-42, with α-chlorocurcumin exhibiting particularly favorable binding characteristics. These findings provide a basis for further investigation of α-halogenated curcumins as potential modulators of Aβ-related molecular processes associated with AD.
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BibTeX
@article{khan2026αhalogenated,
title = {{α-Halogenated Curcumins Enhance the Binding Affinity and Induced Structural Alterations to Amyloid-β Protein in Alzheimer’s Disease}},
author = {Mateen A. Khan and Raja Chinnappan and Sowmya Andole and Mohd. Akif and Tanveer Ahmad Mir and Ahmed Yaqinuddin and Phuong-T T. Pham and Mamoun M. Bader},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209355},
url = {https://www.mdpi.com/1422-0067/27/20/9355},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - α-Halogenated Curcumins Enhance the Binding Affinity and Induced Structural Alterations to Amyloid-β Protein in Alzheimer’s Disease
AU - Mateen A. Khan
AU - Raja Chinnappan
AU - Sowmya Andole
AU - Mohd. Akif
AU - Tanveer Ahmad Mir
AU - Ahmed Yaqinuddin
AU - Phuong-T T. Pham
AU - Mamoun M. Bader
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209355
UR - https://www.mdpi.com/1422-0067/27/20/9355
AB - Amyloid-β (Aβ) aggregation and associated structural changes are central features of Alzheimer’s disease (AD) pathology. In this study, we investigated the binding of α-halogenated curcumins, α-bromocurcumin and α-chlorocurcumin, to Aβ1-42 and examined their effects on the peptide secondary structure using fluorescence spectroscopy and circular dichroism (CD). Both α-halogenated curcumins interacted with Aβ1-42, but their binding properties differed from those of the parent curcumin. α-Chlorocurcumin exhibited a higher binding affinity for Aβ1-42 than curcumin, whereas α-bromocurcumin showed comparatively weaker binding. Temperature-dependent binding studies revealed that the association of α-halogenated curcumins with Aβ1-42 was influenced by temperature, with reduced binding affinity at higher temperatures. Thermodynamic analysis demonstrated favorable free-energy changes for the interactions and revealed that α-halogenation altered the relative enthalpic and entropic contributions to Aβ1-42 binding. CD analysis further showed that binding of the curcumin altered the secondary structure of Aβ1-42. These structural changes were more pronounced in the presence of the α-halogenated derivatives, indicating that halogen substitution influences the interaction and conformational response of Aβ1-42. Molecular docking analysis provided additional insight into the possible binding modes and predicted intermolecular contacts between the α-halogenated curcumin and Aβ1-42. Overall, the findings demonstrate that α-halogenation modulates the binding and structural effects of curcumin derivatives on Aβ1-42, with α-chlorocurcumin exhibiting particularly favorable binding characteristics. These findings provide a basis for further investigation of α-halogenated curcumins as potential modulators of Aβ-related molecular processes associated with AD.
SN - 1422-0067
ER -