Camptothecin and its Analogs Reduce Amyloid-β Production and Amyloid-β 42 -Induced IL-1β Production

Compounds derived from natural products are becoming promising alternative drugs/tools in Alzheimer's disease (AD) therapeutics. From an in-house natural products library, seventeen hits were selected for their inhibitory effect on the production of amyloid-β (Aβ) with IC₅₀ lower than 10 μM without causing obvious toxicity. Among these compounds, camptothecin (CPT) and its analogs showed inhibitory effects on amyloid-β 1-42 (Aβ₄₂) with the IC₅₀ value in the nanomolar range in HEKsw cells and SHSY5Ysw cells. Further studies showed that CPT and its analogs inhibited Aβ₄₂ via a p53 dependent pathway. Meanwhile, CPT and its analogs could also inhibit Aβ₄₂ induced IL-1β production in the THP-1 cells. Taken together, our results indicate that CPT and its analogs would be a promising therapeutic candidates for AD.