Background:
In continuation of our work on Mannich reaction on 8-hydroxyquinoline,
fifteen different combinations of aromatic aldehydes and aniline were subjected to Mannich reaction
from which twelve products (eight Mannich bases, two imines and two intramolecularly cyclized
products with benzofuranone skeleton) were obtained. Among them six compounds (1, 2, 6,
8, 9 and 12) are the new compounds. The structures of the compounds were characterized by UV,
IR, MS and 1H NMR.
Method:
The compounds were tested for the inhibition of pro-inflammatory cytokines tumor necrosis
factor-α (TNF-α) and Interleukin-1β (IL-1β) at a concentration of 25 µg/mL. The cytokines
were produced by THP-1 cells differentiated with PMA for 24hrs and stimulated with LPS for 4
hrs and supernatant were analyzed through ELISA technique.
Results and Discussion:
Compounds 1-5, 8 and 9 inhibited the production of TNF-α and IL-1β.
Compounds 1, 3, and 8 exerted potent inhibitions of TNF-α with 71%, 71%, and 83% inhibition,
respectively. Compounds 1 and 8 significantly inhibited the production of IL-1β with 64% and
78% inhibition, respectively.
Conclusion:
Compounds 1 and 8 significantly inhibited the production of IL-1β with 64% and
78% inhibition, respectively. Notably compound 8 showed the most potent inhibition of these cytokines.
Additionally, the effect of compounds on viability of THP-1 cells was also evaluated.
Moreover, molecular docking was carried out to study the mechanism of inhibition of TNF-α production.
Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones
