Identification of potential inhibitors of Fyn-Kinase from bioactive phytochemicals of Berberis lycium for therapeutic targeting of neurodegenerative disease

Fyn is classified as a member of the Src family of kinases (SFKs), a group of non-receptor tyrosine kinases. It is a critical component of many fundamental central nervous system (CNS) processes. Recently, a connection has been shown between Fyn malfunction and the pathogenic processes exhibited in neurodegenerative conditions, such as Alzheimer's disease (AD), which is a significant factor in worldwide mortality and disability. Due to the rising demographic of elderly individuals, there is a projected increase in incidence of AD in the forthcoming years. This study aims to identify prospective phytochemicals that can be utilized in developing a new protein kinase inhibitor for the therapeutic intervention of AD. The lack of therapeutic interventions capable of preventing the progression of AD is a significant concern thus, it is imperative to identify potential targets. This study employed a virtual screening approach to discover potential Fyn-kinase inhibitors from Berberis lycium (B.ly.) phytoconstituents. Three molecules, Canadine, N-Methyltetrahydroberberine (N-MTHB), and Tetrahydroberberine (THB), were found to have a strong affinity for the binding pocket of Fyn kinase. The docked complexes B.ly. compounds with Fyn underwent all-atom molecular dynamics (MD) simulations to assess their stability and interactions. MD simulation analysis revealed that the identified compounds show promise as potential Fyn inhibitors, which may be implicated in the therapeutic management of AD.