Synthesis of Novel 8-Hydroxyquinoline Derivatives through Mannich Reaction and their Biological Evaluation as Potential Immunomodulatory Agents

Author(s): Shaheen Faizi*, Tahira Sarfaraz, Saima Sumbul, Almas Jabeen, Sobia A. Halim, Mohammad A. Mesaik, Zaheer Ul-Haq*

Journal Name: Medicinal Chemistry

Volume 16 , Issue 4 , 2020

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Graphical Abstract:


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.

Methods: 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.

Keywords: 8-Hydroxyquinoline, aromatic aldehydes, aniline, mannich base, benzofuranone, imine, immunomodulatory, TNF- α and IL-1β, molecular docking.

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Article Details

Year: 2020
Published on: 26 June, 2019
Page: [531 - 543]
Pages: 13
DOI: 10.2174/1573406415666190626121650
Price: $65

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