Carbohydrate-Based NK1R Antagonists with Broad-Spectrum Anticancer Activity

NK1R
antagonists, investigated for the treatment of several pathologies,
have shown encouraging results in the treatment of several cancers.
In the present study, we report on the synthesis of carbohydrate-based
NK1R antagonists and their evaluation as anticancer agents against
a wide range of cancer cells. All of the prepared compounds, derived
from either d-galactose or l-arabinose, have shown
high affinity and NK1R antagonistic activity with a broad-spectrum
anticancer activity and an important selectivity, comparable to Cisplatin.
This strategy has allowed us to identify the galactosyl derivative 14α, as an interesting hit exhibiting significant NK1R
antagonist effect (kinact 0.209 ±
0.103 μM) and high binding affinity for NK1R (IC50 = 50.4 nM, Ki = 22.4 nM by measuring
the displacement of [125I] SP from NK1R). Interestingly,
this galactosyl derivative has shown marked selective cytotoxic activity
against 12 different types of cancer cell lines.