TNF-α and IL-6 inhibitors: Conjugates of N-substituted indole and aminophenylmorpholin-3-one as anti-inflammatory agents

  • Eur J Med Chem. 2017 Nov 10:140:92-103. doi: 10.1016/j.ejmech.2017.09.003.
Palwinder Singh  1 ,  Sukhmeet Kaur  2 ,  Anuradha Sharma  3 ,  Gurcharan Kaur  3 ,  Rajbir Bhatti  4
Affiliations
  • 1. Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, 143005, India. Electronic address: [email protected].
  • 2. Department of Chemistry, UGC Sponsored Centre for Advanced Studies, Guru Nanak Dev University, Amritsar, 143005, India.
  • 3. Department of Biotechnology, Guru Nanak Dev University, Amritsar, 143005, India.
  • 4. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, 143005, India.
PMID: 28923390 DOI: 10.1016/j.ejmech.2017.09.003
Abstract

The conjugates obtained by the combination of indole and aminophenyl morpholinone were screened for TNF-α and IL-6 inhibition in microglial cells. Compound 4 was found to be the most potent anti-inflammatory agent as it reduced LPS induced level of inflammatory cytokines TNF-α and IL-6 by 71% and 53%, respectively. A significant decrease in NO and MMPs release from BV2 cells in culture pretreated with this compound as well as inhibition of nuclear translocation of NF-κB and AP-1 was observed. 75% inhibition of acetic acid induced algesia in swiss albino mice was noticed in the presence of compound 4. Experimental data and molecular docking studies indicate that the compounds are targeting TNF-α, iNOS and IL-6.

Keywords
Anti-inflammatory activity; Indole; Interleukin-6; Lipopolysaccharide; Nitric oxide; Tumor necrosis factor-α.
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