D2AAK1 derivatives as neuroprotective agents: Synthesis and structural and pharmacological evaluation.

Abstract

This study describes 14 novel D2AAK1 derivatives exhibiting enhanced neuroprotective properties. These derivatives were tested for their inhibitory effects on AChE and MAO-B, as well as their effect on cell viability under normal conditions and under oxidative stress. D2AAK1 derivatives show strong cytoprotective effects, increasing cell viability by up to 80% under normal conditions and up to 60% under oxidative stress. These effects may involve modulation of MAPK p38 and Nrf2 pathway interactions, known to promote antioxidant and anti-apoptotic responses. In vivo studies indicated a beneficial effect of the tested derivative on memory processes in the novel object recognition test. These findings identify D2AAK1 derivatives as promising lead compounds for further development as potential treatments of memory deficits.

Key Findings

• 14 novel D2AAK1 derivatives exhibit enhanced neuroprotective properties.
• D2AAK1 derivatives increase cell viability by up to 80% under normal conditions and up to 60% under oxidative stress.
• The neuroprotective effects may involve modulation of MAPK p38 and Nrf2 pathway interactions.
• In vivo studies show beneficial effects on memory processes in the novel object recognition test.

Clinical Significance

Citation

Jastrzębski Michał K, Wójcik Piotr, Pietrzak-Mitura Dianaet al.. D2AAK1 derivatives as neuroprotective agents: Synthesis and structural and pharmacological evaluation. Bioorganic chemistry. 2026-Oct-05.