Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid

Molecules. 2021 Feb 26;26(5):1272. doi: 10.3390/molecules26051272.

Abstract

In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro anti-inflammatory activity. Remarkably high activities were observed for isonicotinates 5-6 and 8a-8b. The compound 5 exhibits an exceptional IC50 value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.

Keywords: ROS inhibitors; anti-inflammatory; isonicotinic acid; molecular docking studies; pyridine carboxylic acid.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Humans
  • Ibuprofen / chemistry
  • Inflammation / drug therapy*
  • Isonicotinic Acids / chemical synthesis*
  • Isonicotinic Acids / chemistry
  • Isonicotinic Acids / pharmacology
  • Molecular Docking Simulation
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / chemistry
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Isonicotinic Acids
  • Reactive Oxygen Species
  • Ibuprofen