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Ru(II)-arene azole complexes as anti-amyloid-β agents.

Ryan M Hacker1, Daniela M Grimard1, Katie A Morgan1

  • 1Department of Chemistry and Biochemistry, SUNY Geneseo, Geneseo, NY, 14454, USA. mwebb@geneseo.edu.

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|August 2, 2024
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Summary
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Ruthenium-arene complexes show promise for Alzheimer's disease (AD) by inhibiting amyloid-beta (Aβ) aggregation and reducing cytotoxicity. The RuBO complex demonstrated significant neuroprotection and low albumin affinity, key for potential neurotherapeutics.

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Area of Science:

  • Medicinal Chemistry
  • Neuroscience
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) aggregation.
  • Anti-amyloid-beta (Aβ) monoclonal antibodies have shown recent clinical success.
  • Metal complexes offer versatile structures for targeting Aβ.

Purpose of the Study:

  • To evaluate ruthenium-arene complexes for modulating Aβ aggregation and cytotoxicity.
  • To assess the stability and Aβ-binding capabilities of these complexes.
  • To identify potential neurotherapeutic agents for Alzheimer's disease.

Main Methods:

  • Evaluation of complex stability in aqueous media.
  • Spectroscopic methods including thioflavin T (ThT) fluorescence, dynamic light scattering (DLS), and transmission electron microscopy (TEM) to assess Aβ modulation.
  • Assessment of affinity for serum albumin.

Main Results:

  • Ruthenium-arene complexes demonstrated exceptional stability in aqueous media.
  • The RuBO complex showed the greatest inhibition of Aβ aggregation, correlating with its Aβ coordination ability.
  • RuBO exhibited the lowest affinity for serum albumin and the greatest inhibition of Aβ-induced cytotoxicity.

Conclusions:

  • Ruthenium-arene complexes, particularly RuBO, are effective in modulating Aβ aggregation and cytotoxicity.
  • RuBO shows potential as a neurotherapeutic agent for Alzheimer's disease due to its neuroprotective properties and favorable pharmacokinetic considerations.
  • Further investigation into RuBO as an anti-Alzheimer's disease agent is warranted.