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Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
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Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
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Bifunctional BODIPY-Clioquinol Copper Chelator with Multiple Anti-AD Properties.

Daniil S Abramchuk1,2, Olga O Krasnovskaya1,2, Alevtina S Voskresenskaya1

  • 1Chemistry Department, Lomonosov Moscow State University, Leninskie Gory 1,3, 119991 Moscow, Russia.

International Journal of Molecular Sciences
|December 30, 2025
PubMed
Summary

Researchers developed BDP-CLQ, a novel bifunctional agent for Alzheimer's disease (AD). This molecule offers optical detection of amyloid-beta (Aβ) fibrils, copper chelation, and multiple anti-AD properties, paving the way for multi-targeted drug development.

Keywords:
Alzheimer’s disease (AD)amyloid beta (Aβ)boron dipyrromethene (BODIPY)clioquinolcopper chelatoroptical visualizationscanning ion conductance microscopy (SICM)

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Area of Science:

  • Neuroscience
  • Medicinal Chemistry
  • Biochemistry

Background:

  • Alzheimer's disease (AD) lacks effective therapies and accurate diagnostic methods.
  • Current therapeutic agents often target only one pathway, limiting efficacy.
  • Multifunctional agents targeting metal ion abnormalities, oxidative stress, and amyloid-beta (Aβ) aggregation are needed.

Purpose of the Study:

  • To develop a novel bifunctional agent for Alzheimer's disease (AD).
  • To create a molecule capable of optical detection of Aβ fibrils and copper chelation.
  • To investigate the potential of a single molecule for multiple anti-AD activities.

Main Methods:

  • Synthesis of a boron dipyrromethene (BODIPY)-based bifunctional copper chelator, BDP-CLQ, incorporating clioquinol.
  • Evaluation of BDP-CLQ's fluorescence response to Aβ.
  • Assessment of BDP-CLQ's copper chelation efficacy.
  • Testing BDP-CLQ's effects on Aβ aggregation, neuronal cell stiffness, and antioxidant activity.

Main Results:

  • BDP-CLQ showed a 3-fold and 5-fold fluorescence increase in the presence of Aβ at specific wavelengths.
  • Effective copper chelation by BDP-CLQ was confirmed (pKd = 16.6 ± 0.3).
  • BDP-CLQ demonstrated significant inhibition of Aβ aggregation, reduced Aβ-induced neuronal cell stiffness, and antioxidant properties.

Conclusions:

  • BDP-CLQ is the first BODIPY-based fluorescent probe with multiple anti-AD activities.
  • It is also the first clioquinol-based probe enabling Aβ optical visualization.
  • This study highlights the potential of clioquinol-based theranostic probes for multi-targeted Alzheimer's disease therapy.