Akademik Veri Yönetim Sistemi
The 49th FEBS Congress, İstanbul, Türkiye, 5 - 09 Temmuz 2025, cilt.15, ss.348, (Özet Bildiri)
Monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) are enzymes targeted in the treatment of some neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s diseases (PD). AD and PD involve complex pathological mechanisms characterized by neuronal degeneration and specific protein aggregates. AD is primarily marked by the presence of amyloid plaques in the spaces between nerve cells, whereas PD is characterized by decreased dopamine (DA) levels in neuronal synapses. In this study, a series of coumarinphthalonitrile derivatives were synthesized, characterized, and evaluated for their inhibitory activity on MAO-A and MAO-B for treatment of AD and PD. Among the investigatedcompounds, 4-[7-oxy-3-phenylcoumarin]phthalonitrile (K1) selectively inhibited the MAO-B activity with an IC50 value of 80 nM (MAO-B specific Selectivity Index (SI) is 1250). Additionally, the mechanism and the reversibility of this inhibition were further analyzed. Molecular docking studies were performed to predict the binding modes of the most active compounds. The results suggest that coumarin-phthalonitrile derivatives could serve as promising candidates for further development of selective MAO-B inhibitors targeting neurodegenerative disorders, including AD and PD.