Work

Filicinic acid based meroterpenoids from Hypericum elodeoides and their anti-Alzheimer’s disease effects

Year: 2024

Type: article

Abstract: (±)-Elodeoidileons A-L ( 1 – 12 ), 12 pairs of previously undescribed filicinic acid based meroterpenoids were isolated from Hypericum elodeoides with unique linear or angular 6/6/6 ring core. Modern spectroscopic techniques, modified Mosher’s method and quantum chemical calculations were used to identify the planner structures and configurations of 1 – 12 . Additionally, the potential biosynthetic pathways for 1 – 12 were anticipated. Moreover, biological activity assessments suggested that 1a , 5a , and 11b could activate Retinoid X receptor-α (RXRα) transcription and enhance the ATP-binding cassette transporter A1 (ABCA1) protein’s expression. Fluorescence titration assay suggested that 1a might have a direct interaction with the RXRα-LBD protein, with an estimated K d value of 5.85 μM. Moreover, molecular docking study confirmed the binding of 1a to RXRα and further validated by cellular thermal shift assay (CETSA). Thus, compound 1a may promote β-amyloid (Aβ) clearance by targeting RXRα and upregulating the expression of the ABCA1 protein, showing promise as anti-Alzheimer’s agent.

Source: Bioorganic Chemistry

DOI: 10.1016/j.bioorg.2024.107787