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Cardiotoxicity and ROS Protection Assessment of three Structure-Related N-Acylhydrazones with Potential for the Treatment of Neurodegenerative Diseases. | LitMetric

Cardiotoxicity and ROS Protection Assessment of three Structure-Related N-Acylhydrazones with Potential for the Treatment of Neurodegenerative Diseases.

Chem Biodivers

Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro (PUC-Rio), Rio de Janeiro, 22451-900, Brazil Tel.

Published: March 2024

AI Article Synopsis

  • - The senescence process leads to oxidative damage and increased metal levels in the heart and brain, which are linked to diseases like Alzheimer's and Parkinson's, prompting research into compounds that may mitigate these effects.
  • - Three N-acylhydrazones were tested for their ability to prevent oxidative stress while ensuring they don't cause heart toxicity, which is crucial since the target population often has heart issues.
  • - Among the compounds, INHHQ showed strong antioxidant effects and cardioprotective properties but was also the most toxic, while X1INH demonstrated potential cardioprotection without significant toxicity, highlighting the need for a balance between effectiveness and safety in drug development.

Article Abstract

The senescence process is associated with accumulated oxidative damage and increased metal concentration in the heart and brain. Besides, abnormal metal-protein interactions have also been linked with the development of several conditions, including Alzheimer's and Parkinson's diseases. Over the years we have described a series of structure-related compounds with different activities towards models of such diseases. In this work, we evaluated the potential of three N-acylhydrazones (INHHQ: 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone, HPCIH: pyridine-2-carboxaldehyde isonicotinoyl hydrazone and X1INH: 1-methyl-1H-imidazole-2-carboxaldehyde isonicotinoyl hydrazone) to prevent oxidative stress in cellular models, with the dual intent of being active on this pathway and also to confirm their lack of cardiotoxicity as an important step in the drug development process, especially considering that the target population often presents cardiovascular comorbidity. The 8-hydroxyquinoline-contaning compound, INHHQ, exhibits a significant cardioprotective effect against hydrogen peroxide and a robust antioxidant activity. However, this compound is the most toxic to the studied cell models and seems to induce oxidative damage on its own. Interestingly, although not possessing a phenol group in its structure, the new-generation 1-methylimidazole derivative X1INH showed a cardioprotective tendency towards H9c2 cells, demonstrating the importance of attaining a compromise between activity and intrinsic cytotoxicity when developing a drug candidate.

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Source
http://dx.doi.org/10.1002/cbdv.202400356DOI Listing

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