Molecular orbital theory applied to the study of nonsteroidal anti-inflammatory drug efficiency

Free Radic Biol Med. 1999 May;26(9-10):1261-6. doi: 10.1016/s0891-5849(98)00324-4.

Abstract

Using a simple quantum mechanical method, we calculated the energy of the highest-occupied molecular orbital (E(HOMO)) of three groups of anti-inflammatory compounds, and we have found correlations between E(HOMO) of these molecules and experimental data previously reported on (1) inhibition of sheep-vesicular-gland prostaglandin cyclooxygenase by phenolic compounds, (2) inhibition of prostaglandin cyclooxygenase in mouse macrophages by salicylates, benzoates and phenols, and (3) peroxyl-radical scavenging and radioprotection of a bacterial virus by NSAID drugs, including metiazinic acid, sulindac, D-penicillamine, piroxicam, indomethacin, benoxaprofen, and aspirin. Our correlations using a systematic evaluation of the HOMO energies can be of predictive value in the search for new anti-inflammatory drugs as well as for new radioprotectors.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Bacteriophages / drug effects
  • Bacteriophages / radiation effects
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • In Vitro Techniques
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Mice
  • Models, Chemical
  • Quantum Theory
  • Sheep
  • Structure-Activity Relationship
  • Thermodynamics

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Free Radical Scavengers