Drug Development.

Area of Science:

• Medicinal Chemistry
• Neuroscience
• Drug Discovery

Background:

• Alzheimer's disease (AD) is a leading cause of dementia, affecting over 55 million people globally.
• Lack of effective therapies for AD necessitates novel treatment strategies.
• Targeting amyloid-beta (Aβ) aggregation is a promising therapeutic approach for AD.

Purpose of the Study:

• To design and synthesize novel selenium-based small molecules, N-benzylphenoselenazines.
• To evaluate the potential of these compounds in inhibiting Aβ aggregation and neurotoxicity.
• To assess their antioxidant activity and cytotoxicity for potential Alzheimer's disease treatment.

Main Methods:

• Synthesis of N-benzylphenoselenazine library via optimized chemical protocols.
• In vitro evaluation of anti-Aβ40 aggregation using thioflavin-T fluorescence and electron microscopy.
• Assessment of antioxidant activity and cytotoxicity in mouse hippocampal neuronal cells.

Main Results:

• Successful synthesis of N-benzylphenoselenazines with yields ranging from 23-89%.
• Compounds demonstrated significant Aβ40 aggregation inhibition (26-85%) and antioxidant activity (23-80.5%).
• No cytotoxicity observed in mouse hippocampal HT22 neuronal cells.

Conclusions:

• Novel selenium-based N-benzylphenoselenazines show promise in reducing Aβ40 aggregation.
• These compounds possess antioxidant properties, indicating potential as disease-modifying agents for Alzheimer's disease.
• Further research into these small molecules could lead to new therapeutic options for AD.