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Updated: Jul 16, 2026

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
16:07

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method

Published on: September 16, 2017

A chromone analog inhibits TNF-alpha induced expression of cell adhesion molecules on human endothelial cells via

Sarvesh Kumar1, Brajendra K Singh, Anil K Pandey

  • 1Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, University of Delhi Campus (North), Mall Road, Delhi 110 007, India.

Bioorganic & Medicinal Chemistry
|February 27, 2007
PubMed

Insights

New chromone derivatives were synthesized to inhibit cell adhesion molecules involved in inflammatory diseases. The most potent compound, ethyl trans-3-(4-oxo-4H-1-benzopyran-3-yl)-acrylate (8a), effectively blocked key inflammatory markers and neutrophil adhesion by inhibiting NF-kappaB activation.

Area of Science:

  • Medicinal Chemistry
  • Immunology
  • Biochemistry

Background:

  • Cellular adhesion molecules (e.g., ICAM-1, VCAM-1, E-selectin) mediate leukocyte-endothelial interactions crucial in inflammatory and immune diseases.
  • Inhibitors of these interactions are sought as therapeutic agents for inflammatory conditions.

Purpose of the Study:

  • To design, synthesize, and evaluate novel chromone derivatives as inhibitors of cellular adhesion molecules.
  • To investigate the structure-activity relationships of these compounds concerning ICAM-1 inhibition and lipid peroxidation.
  • To assess the most potent compound's efficacy in inhibiting key inflammatory markers and its mechanism of action.

Main Methods:

  • Synthesis of chromone derivatives with alkoxycarbonylvinyl units at the C-3 position.
  • Evaluation of ICAM-1 inhibitory activity on human endothelial cells.
  • Assessment of effects on NADPH-catalyzed rat microsomal lipid peroxidation.
  • Inhibition assays for TNF-alpha induced expression of ICAM-1, VCAM-1, and E-selectin.
  • Cell-adhesion assays to measure neutrophil adhesion to endothelial cells.
  • Investigation of NF-kappaB activation status.

Main Results:

  • Structure-activity relationship studies indicated the importance of alkyl chain length and unsaturation in the alcohol moiety for inhibitory activity.
  • Ethyl trans-3-(4-oxo-4H-1-benzopyran-3-yl)-acrylate (8a) emerged as the most potent inhibitor.
  • Compound 8a demonstrated significant, concentration-dependent inhibition of TNF-alpha induced ICAM-1, VCAM-1, and E-selectin expression.
  • Compound 8a effectively blocked neutrophil adhesion to endothelial cells.
  • Compound 8a significantly inhibited TNF-alpha induced activation of NF-kappaB.

Conclusions:

  • Novel chromone derivatives, particularly compound 8a, show significant potential as inhibitors of key cellular adhesion molecules involved in inflammation.
  • Compound 8a's mechanism involves the inhibition of NF-kappaB activation, leading to reduced expression of adhesion molecules and decreased neutrophil adhesion.
  • These findings support the development of chromone-based therapeutics for inflammatory diseases.

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