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Allosecurinine Derivative with Two Michael Acceptors Activates Keap1-Nrf2 Pathway
Seoyoung Kim1, Rium Kim2,3, Taejin Chu2,3
1Department of Chemistry, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 34141, Republic of Korea.
Journal of Agricultural and Food Chemistry
|February 11, 2026
Summary
Securinega alkaloid derivatives were synthesized to target the Keap1-Nrf2 pathway for neurodegenerative diseases. A potent derivative activated Nrf2, reduced inflammation, and showed potential for treating these conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Organic Chemistry
Background:
- Neurodegenerative diseases are driven by oxidative stress and neuroinflammation.
- The Keap1-Nrf2 pathway is a key therapeutic target for these conditions.
Purpose of the Study:
- To derivatize securinega alkaloids to activate the Keap1-Nrf2 pathway.
- To evaluate the potential of these derivatives in treating neuroinflammation and neurodegenerative diseases.
Main Methods:
- Securinega alkaloids were modified by introducing a 1,4-conjugated Michael acceptor.
- The most potent derivative, 4,5-dehydro-6-oxoallosecurinine, was identified.
- Its effects on Nrf2 activation, gene expression, and inflammatory markers were assessed in microglial cells.
Main Results:
- 4,5-dehydro-6-oxoallosecurinine demonstrated potent Nrf2 activation.
- The compound induced antioxidant and cytoprotective gene expression.
- It significantly reduced nitric oxide and pro-inflammatory cytokine levels in LPS-stimulated microglia.
Conclusions:
- Securinega alkaloid derivatives are promising Nrf2 activators.
- These compounds warrant further investigation for neuroinflammatory and neurodegenerative disease therapies.
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