Molecular orbital theory applied to the study of nonsteroidal anti-inflammatory drug efficiency.
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.
Zoete
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V
Laboratoire de Chimie Organique Physique, Université des Sciences et Technologies de Lille, CNRS UA 351, Villeneuve d'Ascq, France.
Bailly
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F
Maglia
F
F
Rougée
M
M
Bensasson
R V
RV
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D001435:Bacteriophages / Q000187:drug effects / Q000528:radiation effects; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008956:Models, Chemical; D011789:Quantum Theory; D012756:Sheep; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers